Descriptor: "MESH : Transcription Factors" - Searchworks@Jio Institute Digital Library Search Results

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44 results on '"MESH : Transcription Factors"'

1. Truncation of PITX2 differentially affects its activity on physiological targets

Author: Véronique Vieira, Maurice Menasche, James P. Herman, Thierry Brue, Alain Enjalbert, Marc Abitbol, Marie-Helene Quentien, Jean-Louis Dufier, Centre de recherche en neurobiologie - neurophysiologie de Marseille (CRN2M), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche thérapeutique en ophtalmologie, Université Paris Descartes - Paris 5 (UPD5)-EA2502, EA no 2502 du ministère de la Recherche, de l'Enseignement Supérieur et la Technologie, Université Paris Descartes - Paris 5 (UPD5)-CERTO, Service d'ophtalmologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Centre d'étude et de recherche thérapeutiques en ophtalmologie, Université Paris Descartes - Paris 5 (UPD5), Aix Marseille Université (AMU) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5) - EA2502, Université Paris Descartes - Paris 5 (UPD5) - CERTO, Assistance publique - Hôpitaux de Paris (AP-HP) - CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: MESH : Cell Line, MESH : Transcription Factors, MESH : Transcription Factor Pit-1, Mutant, Electrophoretic Mobility Shift Assay, MESH : Blotting, Western, MESH : Promoter Regions, Genetic, medicine.disease_cause, MESH : Pituitary Gland, 0302 clinical medicine, Endocrinology, MESH : Prolactin, MESH: Pituitary Gland, MESH: Human Growth Hormone, MESH: Animals, MESH : Transcriptional Activation, MESH : Homeodomain Proteins, Eye Abnormalities, Promoter Regions, Genetic, 0303 health sciences, Mutation, MESH: Anterior Eye Segment, Human Growth Hormone, Eye Diseases, Hereditary, MESH: Transcription Factors, Transfection, MESH: Eye Abnormalities, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Cell biology, MESH : Electrophoretic Mobility Shift Assay, Pituitary Gland, MESH : Mutation, Transcription Factor Pit-1, hormones, hormone substitutes, and hormone antagonists, Transcriptional Activation, congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, MESH: Mutation, Blotting, Western, MESH: Prolactin, Biology, MESH : Anterior Eye Segment, Cell Line, [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], 03 medical and health sciences, stomatognathic system, Anterior Eye Segment, Internal medicine, MESH : Eye Abnormalities, MESH: Promoter Regions, Genetic, MESH: Homeodomain Proteins, medicine, MESH: Blotting, Western, Animals, Humans, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], MESH : Human Growth Hormone, Molecular Biology, Transcription factor, Gene, 030304 developmental biology, Homeodomain Proteins, Reporter gene, MESH: Humans, POU domain, MESH : Humans, Promoter, MESH: Cell Line, Prolactin, stomatognathic diseases, MESH: Electrophoretic Mobility Shift Assay, 030221 ophthalmology & optometry, MESH: Transcriptional Activation, MESH : Animals, sense organs, MESH: Transcription Factor Pit-1, Transcription Factors
Abstract: International audience; The bicoid-like transcription factor PITX2 has been previously described to interact with the pituitary-specific POU homeodomain factor POU1F1 (human ortholog of PIT-1) to achieve cell-specific expression of prolactin (PRL) and GH in pituitary somatolactotroph cells. In this work, we have investigated the functional properties of three PITX2 mutants reported in Axenfeld-Rieger syndrome patients relative to the regulation of these genes, using reporter genes under the control of human PRL (hPRL), hGH, or POU1F1 promoters transfected in nonpituitary and pituitary cell lines. Among the three mutations studied, Y167X and E101X introduce a premature stop codon, and F104L leads to an amino acid substitution. While PITX2(E101X) is not expressed in the cells following transfection, and PITX2(F104L) is functionally inactive, the PITX2(Y167X) mutant keeps its DNA-binding capacity and displays a markedly enhanced activation of the hPRL and POU1F1 promoters, but not of the hGH promoter. Y167X is the first mutation of PITX2 described to result in a differential effect on the activation of its different physiological targets, hPRL and POU1F1 on one hand and hGH on the other hand. The differential effect of the Y167X mutation might be linked to an interaction of PITX2 with different transcription factors or cofactors when bound to the hPRL and POU1F1 or the hGH promoters. These results might form the basis for the identification of the PITX2 protein complex necessary for the differential GH or PRL expression.
Published: 2010
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2. miR-661 expression in SNAI1-induced epithelial to mesenchymal transition contributes to breast cancer cell invasion by targeting Nectin-1 and StarD10 messengers

Author: Khalil Arar, Christina Laurini, Michèle Sabbah, Laurent Vallar, Michèle Moes, Charles-Henri Lecellier, Evelyne Friederich, A. Le Bechec, Guillaume Vetter, Anne Saumet, Charles Theillet, Le Ster, Yves, Cytoskeleton and Cell Plasticity Lab, Université du Luxembourg (Uni.lu), Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre de Recherche Publique- Santé, Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sigma-Aldrich - Evry GENEPOLE, Sigma-Aldrich, Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), This work was supported by grants from the Fond National de la Recherche (FNR) du Luxembourg, (BIOSAN), the Fondation Luxembourgeoise Contre le Cancer, Human Frontier Science Program (RGP0058/2005), INSERM and CNRS, France. A. Saumet is a recipient of a fellowship from the Ministère de la Culture, de l'Enseignement Supérieur et de la Recherche, Luxembourg (BFR 08/046). M. Moes and A. Le Béchec are supported by AFR grants from the Fond National de la Recherche, Luxembourg., CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Université du Luxembourg ( Uni.lu ), Institut de recherche en cancérologie de Montpellier ( IRCM ), Université Montpellier 1 ( UM1 ) -CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Centre de Recherche Saint-Antoine ( CR Saint-Antoine ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de Génétique Moléculaire de Montpellier ( IGMM ), and Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: SNAI1, Cancer Research, MESH : RNA, Messenger, MESH : Transcription Factors, MESH : Cell Dedifferentiation, Gene Expression, MESH : Breast Neoplasms, Biochemistry, biophysics & molecular biology [F05] [Life sciences], Validation Studies as Topic, MESH : RNA, Small Interfering, medicine.disease_cause, Bioinformatics, MESH : Neoplasm Invasiveness, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Metastasis, 0302 clinical medicine, MESH : Tumor Cells, Cultured, MESH : Validation Studies as Topic, EMT/miR-661/ SNAI1/StarD10/Nectin-1/breast cancer cell invasion, MESH: RNA, Small Interfering, Tumor Cells, Cultured, MESH : Female, RNA, Small Interfering, Biochimie, biophysique & biologie moléculaire [F05] [Sciences du vivant], Oligonucleotide Array Sequence Analysis, 0303 health sciences, EMT, MESH: Transcription Factors, MESH: Gene Expression Regulation, Neoplastic, MESH : Epithelial Cells, Gene Expression Regulation, Neoplastic, MESH : Oligonucleotide Array Sequence Analysis, MESH: Epithelial Cells, 030220 oncology & carcinogenesis, MESH: Cell Adhesion Molecules, Female, Breast disease, StarD10, Nectin-1, MESH: Gene Expression, MESH : Gene Expression Regulation, Neoplastic, Nectins, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, MESH: Phosphoproteins, MESH : Cell Adhesion Molecules, MESH: Gene Expression Profiling, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, microRNA, Genetics, medicine, Humans, Gene silencing, Neoplasm Invasiveness, RNA, Messenger, MESH: Tumor Cells, Cultured, Epithelial–mesenchymal transition, Molecular Biology, MESH: RNA, Messenger, 030304 developmental biology, breast cancer cell invasion, MESH: Validation Studies as Topic, MESH: Humans, MESH : Gene Expression Profiling, Gene Expression Profiling, MESH : Humans, Cancer, Epithelial Cells, Mesenchymal Stem Cells, MESH: Neoplasm Invasiveness, Cell Dedifferentiation, Phosphoproteins, medicine.disease, MESH: Cell Dedifferentiation, miR-661, MESH : Gene Expression, MESH : MicroRNAs, MicroRNAs, Retraction Note, MESH: Mesenchymal Stem Cells, MESH: Oligonucleotide Array Sequence Analysis, Cancer research, Snail Family Transcription Factors, MESH : Phosphoproteins, MESH : Mesenchymal Stem Cells, Carcinogenesis, Cell Adhesion Molecules, MESH: MicroRNAs, MESH: Female, MESH: Breast Neoplasms, Transcription Factors
Abstract: 4; International audience; Epithelial to mesenchymal transition (EMT) is a key step toward metastasis. MCF7 breast cancer cells conditionally expressing the EMT master regulator SNAI1 were used to identify early expressed microRNAs (miRNAs) and their targets that may contribute to the EMT process. Potential targets of miRNAs were identified by matching lists of in silico predicted targets and of inversely expressed mRNAs. MiRNAs were ranked based on the number of predicted hits, highlighting miR-661, a miRNA with so far no reported role in EMT. MiR-661 was found required for efficient invasion of breast cancer cells by destabilizing two of its predicted mRNA targets, the cell-cell adhesion protein Nectin-1 and the lipid transferase StarD10, resulting, in turn, in the downregulation of epithelial markers. Reexpression of Nectin-1 or StarD10 lacking the 3'-untranslated region counteracted SNAI1-induced invasion. Importantly, analysis of public transcriptomic data from a cohort of 295 well-characterized breast tumor specimen revealed that expression of StarD10 is highly associated with markers of luminal subtypes whereas its loss negatively correlated with the EMT-related, basal-like subtype. Collectively, our non-a priori approach revealed a nonpredicted link between SNAI1-triggered EMT and the down-regulation of Nectin-1 and StarD10 through the up-regulation of miR-661, which may contribute to the invasion of breast cancer cells and poor disease outcome.
Published: 2010
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3. GoArrays: highly dynamic and efficient microarray probe design

Author: Pierre Peyret, David E. Hill, Cécile Militon, Sébastien Rimour, Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Informatique, de Modélisation et d'optimisation des Systèmes (LIMOS), SIGMA Clermont (SIGMA Clermont)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Ecole Nationale Supérieure des Mines de St Etienne-Centre National de la Recherche Scientifique (CNRS)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP), This work was supported by a grant from the CNRS ‘puces à ADN'. S.R. and C.M. were supported by a grant from ‘Ministère de l'éducation, de la recherche et de la technologie'., Technische Hoschschule, University of Applied Sciences [Darmstadt], Institut méditerranéen d'océanologie (MIO), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université de Toulon (UTLN), Conception, Ingénierie et Développement de l'Aliment et du Médicament (CIDAM), Université d'Auvergne - Clermont-Ferrand I (UdA), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Centre National de la Recherche Scientifique (CNRS)-Université d'Auvergne - Clermont-Ferrand I (UdA), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université d'Auvergne - Clermont-Ferrand I (UdA)-SIGMA Clermont (SIGMA Clermont)-Ecole Nationale Supérieure des Mines de St Etienne (ENSM ST-ETIENNE)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Microorganismes : Génome et Environnement ( LMGE ), Université Blaise Pascal - Clermont-Ferrand 2 ( UBP ) -Centre National de la Recherche Scientifique ( CNRS ) -Université d'Auvergne - Clermont-Ferrand I ( UdA ), Laboratoire d'Informatique, de Modélisation et d'optimisation des Systèmes ( LIMOS ), Centre National de la Recherche Scientifique ( CNRS ) -Sigma CLERMONT ( Sigma CLERMONT ) -Université d'Auvergne - Clermont-Ferrand I ( UdA ) -Université Blaise Pascal - Clermont-Ferrand 2 ( UBP ), and Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH : Transcription Factors, probe design, Microarray, MESH: Oligonucleotide Probes, MESH : Equipment Design, Quantitative Biology - Quantitative Methods, Biochemistry, Software, MESH: Animals, [ SDV.BIBS ] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Biopuces ADN, Quantitative Methods (q-bio.QM), MESH : Algorithms, MESH : Encephalitozoon cuniculi, ComputingMilieux_MISCELLANEOUS, Oligonucleotide Array Sequence Analysis, Genetics, 0303 health sciences, biology, Biological modeling, Equipment Design, MESH: Transcription Factors, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Computer Science Applications, MESH : Oligonucleotide Array Sequence Analysis, Computational Mathematics, Computational Theory and Mathematics, Computer-Aided Design, Software design, MESH : Software, MESH: Encephalitozoon cuniculi, DNA microarray, Encephalitozoon cuniculi, Algorithms, algorithme, Statistics and Probability, MESH : Computer-Aided Design, MESH: Algorithms, Computational biology, génomique, Intracellular pathogen, MESH: Gene Expression Profiling, MESH: Software, 03 medical and health sciences, [ INFO.INFO-BI ] Computer Science [cs]/Bioinformatics [q-bio.QM], Animals, microbiologie, Molecular Biology, 030304 developmental biology, [ SDE.BE ] Environmental Sciences/Biodiversity and Ecology, 030306 microbiology, Oligonucleotide, business.industry, Gene Expression Profiling, MESH : Gene Expression Profiling, transcriptomique, MESH: Computer-Aided Design, biology.organism_classification, MESH : Oligonucleotide Probes, FOS: Biological sciences, MESH: Oligonucleotide Array Sequence Analysis, MESH : Animals, DNA microarrays, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], [SDE.BE]Environmental Sciences/Biodiversity and Ecology, Oligonucleotide Probes, business, Transcription Factors, MESH: Equipment Design
Abstract: Motivation: The use of oligonucleotide microarray technology requires a very detailed attention to the design of specific probes spotted on the solid phase. These problems are far from being commonplace since they refer to complex physicochemical constraints. Whereas there are more and more publicly available programs for microarray oligonucleotide design, most of them use the same algorithm or criteria to design oligos, with only little variation. Results: We show that classical approaches used in oligo design software may be inefficient under certain experimental conditions, especially when dealing with complex target mixtures. Indeed, our biological model is a human obligate parasite, the microsporidia Encephalitozoon cuniculi. Targets that are extracted from biological samples are composed of a mixture of pathogen transcripts and host cell transcripts. We propose a new approach to design oligonucleotides which combines good specificity with a potentially high sensitivity. This approach is original in the biological point of view as well as in the algorithmic point of view. We also present an experimental validation of this new strategy by comparing results obtained with standard oligos and with our composite oligos. A specific E.cuniculi microarray will overcome the difficulty to discriminate the parasite mRNAs from the host cell mRNAs demonstrating the power of the microarray approach to elucidate the lifestyle of an intracellular pathogen using mix mRNAs. Availability: Our method is implemented in the GoArrays software, available at http://www.isima.fr/bioinfo/goarrays/ Contact: rimour@isima.fr for computing part, and pierre.peyret@univ-bpclermont.fr for collaborative projects.
Published: 2004
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4. A key role for stress-induced satellite III transcripts in the relocalization of splicing factors into nuclear stress granules

Author: Jamal Tazi, Alexandra Metz, Johann Soret, Caroline Jolly, Claire Vourc'h, Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), INSERM U823, équipe 10 (Stress et Dynamique de l'Organisation du Génome), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Souchier, Catherine, Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institut d'oncologie/développement Albert Bonniot de Grenoble ( INSERM U823 ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de Génétique Moléculaire de Montpellier ( IGMM ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut National de la Santé et de la Recherche Médicale (INSERM)-EFS-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), and Institut National de la Santé et de la Recherche Médicale (INSERM)-EFS-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-EFS-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)
Subjects: MESH : Transcription Factors, MESH : Hela Cells, MESH: 3T3 Cells, MESH: Tubulin, MESH : Cell Cycle Proteins, 0302 clinical medicine, Heat Shock Transcription Factors, MESH : Leupeptins, Transcription (biology), MESH : Cell Nucleus Structures, MESH: Animals, Satellite III transcripts, HSF1, MESH: HSP70 Heat-Shock Proteins, MESH : Ubiquitin, 0303 health sciences, MESH : Ribonucleoproteins, Small Nuclear, Serine-Arginine Splicing Factors, MESH : Histone Deacetylases, Nuclear Proteins, RNA-Binding Proteins, MESH : Protein Binding, MESH: Transcription Factors, MESH : Tubulin, MESH : HSP90 Heat-Shock Proteins, Ribonucleoproteins, Small Nuclear, MESH : Heat-Shock Response, MESH: DNA, Satellite, DNA-Binding Proteins, Heat shock, RNA splicing, RNA Polymerase II, MESH : RNA Polymerase II, MESH : RNA Splicing, MESH : DNA-Binding Proteins, MESH: Molecular Chaperones, MESH: Acetylation, MESH : 3T3 Cells, MESH : Protein Folding, MESH: Ubiquitin, RNA Splicing, MESH: Protein Folding, MESH : RNA-Binding Proteins, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, DNA, Satellite, Biology, MESH : Acetylation, MESH: Phosphoproteins, 03 medical and health sciences, MESH: Cell Cycle Proteins, SR protein, Stress granule, Heat shock protein, MESH : Mice, MESH: Adenosine Triphosphatases, MESH: HSP90 Heat-Shock Proteins, Humans, MESH: Protein Binding, HSP70 Heat-Shock Proteins, Nuclear stress granules, snRNP, MESH: Cell Nucleus Structures, MESH: Mice, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, 030304 developmental biology, MESH : DNA, Satellite, MESH: Humans, MESH : Adenosine Triphosphatases, [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology, MESH: Ribonucleoproteins, Small Nuclear, MESH : Humans, MESH : Molecular Chaperones, MESH : Nuclear Proteins, MESH : HSP70 Heat-Shock Proteins, MESH: Leupeptins, Cell Biology, Phosphoproteins, Molecular biology, Cell Nucleus Structures, MESH: RNA Polymerase II, MESH: Hela Cells, MESH: Histone Deacetylases, Heat shock factor, MESH: RNA-Binding Proteins, MESH: Heat-Shock Response, MESH : Animals, MESH : Phosphoproteins, MESH: RNA Splicing, MESH: Nuclear Proteins, SR proteins, MESH: DNA-Binding Proteins, 030217 neurology & neurosurgery, HeLa Cells, Transcription Factors
Abstract: International audience; Exposure of cells to stressful conditions results in the rapid synthesis of a subset of specialized proteins termed heat shock proteins (HSPs) which function in protecting the cell against damage. The stress-induced activation of hsp genes is controlled by the heat shock transcription factor 1 (HSF1). At the cellular level, one of the most striking effects of stress is the rapid and reversible redistribution of HSF1 into a few nuclear structures termed nuclear stress granules which form primarily on the 9q12 locus in humans. Within these structures, HSF1 binds to satellite III repeated elements and drives the RNA polymerase II-dependent transcription of these sequences into stable RNAs which remain associated with the 9q12 locus for a certain time after synthesis. Other proteins, in particular splicing factors, were also shown to relocalize to the granules upon stress. Here, we investigated the role of stress-induced satellite III transcripts in the relocalization of splicing factors to the granules. We show that the recruitment of the two serine/arginine-rich (SR) proteins SF2/ASF and SRp30c requires the presence of stress-induced satellite III transcripts. In agreement with these findings, we identified the second RNA-recognition motif (RRM2) of hSF2/ASF as the motif required for the targeting to the granules, and we showed by immunoprecipitation that the endogenous hSF2/ASF protein is present in a complex with satellite III transcripts in stressed cells in vivo. Interestingly, satellite III transcripts also immunoprecipitate together with small nuclear ribonucleoproteins (snRNPs) in vivo whereas the intronless hsp70 transcripts do not, supporting the proposal that these transcripts are subject to splicing. Altogether, these data highlight the central role for satellite III transcripts in the targeting and/or retention of splicing factors into the granules upon stress.
Published: 2004
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5. Type II TGFβ receptor modulates chondrocyte phenotype

Author: Elise Duval, Sylvain Leclercq, Catherine Baugé, Philippe Galéra, Nicolas Girard, Karim Boumediene, David Ollitrault, Normandie Université ( NU ), Microenvironnement cellulaire et pathologie ( MILPAT ), Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Département de chirurgie orthopédique, Clinique Saint Martin, Normandie Université (NU), Microenvironnement et Pathologies du Cartilage (BioConnecT), Microenvironnement cellulaire et pathologie (MILPAT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Département de chirurgie orthopédique [Hôpital privé Saint Martin Caen], and Hôpital Privé Saint Martin Caen
Subjects: Cartilage, Articular, MESH : Bone Marrow, Aging, MESH : RNA, Messenger, MESH : Transcription Factors, MESH : Receptors, Transforming Growth Factor beta, MESH : Chondrogenesis, MESH : Alginates, MESH : Blotting, Western, Osteoarthritis, Hip, 0302 clinical medicine, MESH: Aggrecans, MESH: Osteoarthritis, MESH : Collagen Type II, Cells, Cultured, Regulation of gene expression, Aged, 80 and over, 0303 health sciences, [ SDV.MHEP.PHY ] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], MESH: Bone Marrow Cells, Cell Differentiation, General Medicine, MESH: Transcription Factors, Middle Aged, Cell biology, MESH : Phenotype, medicine.anatomical_structure, Phenotype, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, 030220 oncology & carcinogenesis, MESH: Alginates, Disease Progression, MESH: Bone Marrow, MESH: Receptors, Transforming Growth Factor beta, MESH : Cell Differentiation, MESH: Chondrogenesis, Signal Transduction, MESH: Cell Differentiation, Blotting, Western, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, MESH: Phenotype, Real-Time Polymerase Chain Reaction, Chondrocyte, Article, MESH : Chondrocytes, MESH : Cartilage, [ SDV.MHEP.RSOA ] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, 03 medical and health sciences, Transforming Growth Factor beta2, Chondrocytes, MESH: Chondrocytes, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], MESH : Aggrecans, Gene silencing, MESH: Blotting, Western, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, RNA, Messenger, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Aggrecan, MESH: Transforming Growth Factor beta, 030304 developmental biology, MESH: RNA, Messenger, Aged, MESH: Humans, [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology, Mesenchymal stem cell, MESH : Humans, MESH: Collagen Type II, Chondrogenesis, Molecular biology, MESH : Osteoarthritis, MESH : Transforming Growth Factor beta, Gene Expression Regulation, MESH: Cartilage, Ectopic expression, Geriatrics and Gerontology, Transforming growth factor, MESH : Bone Marrow Cells
Abstract: International audience; Aging is one of the major risk factors of osteoarthritis. This pathology during which chondrocytes undergo modifications of their phenotype may result from alteration of transforming growth factor β (TGFβ) signaling. This study investigates the role of TGFβ response in the process of chondrocyte dedifferentiation/redifferentiation. Dedifferentiation was induced by successive passages of human articular chondrocytes, whereas their redifferentiation was performed by three-dimensional culture in alginate. Human mesenchymal stem cells were obtained from bone marrow and differentiated into chondrocyte-like phenotype by three-dimensional culture, embedded in the same scaffold. Protein and mRNA levels were analyzed by Western blot and real-time reverse transcription PCR. Regulatory mechanism was investigated using specific inhibitors (mithramycin), mRNA silencing or decoy oligonucleotides, and expression vectors. Chondrocyte dedifferentiation interfered with TGFβ signaling by decreasing TβRII mRNA and protein levels and subsequent TGFβ response. TβRII ectopic expression in passaged chondrocytes permitted to increase the expression of several matrix genes, such as aggrecan or type II collagen. Redifferentiation of passaged chondrocytes permitted to restore, at least in part, TβRII expression and was related to differentiation of human bone marrow mesenchymal stem cells toward chondrocytes, where both specific protein 1 (Sp1) and TβRII mRNA levels were increased. Moreover, Sp1 manipulation by silencing or ectopic expression and pharmacologic inhibition revealed a link between expression levels of this transcriptional factor, which is crucial for constitutive expression of TβRII in cartilage, and TGFβ response. Therefore, these data permit us to suggest an important role of TβRII expression in the maintenance of chondrocyte phenotype, which is altered with age, and bring new insights in our understanding of chondrogenesis process.
Published: 2013
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6. Six homeoproteins directly activate Myod expression in the gene regulatory networks that control early myogenesis

Author: Frédéric Relaix, Christine Laclef, Josiane Demignon, Didier Rocancourt, Mounia Lagha, Marc Santolini, Margaret Buckingham, Claire Niro, Pascal Maire, Julien Pujol, Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique Statistique de l'ENS (LPS), Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Département de Biologie du Développement, Université Paris Diderot - Paris 7 (UPD7)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris], d'Eggis, Gilles, Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Sorbonne Université (SU), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Association française contre les myopathies ( AFM-Téléthon ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Physique Statistique de l'ENS ( LPS ), Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris ( FRDPENS ), and Centre National de la Recherche Scientifique ( CNRS ) -École normale supérieure - Paris ( ENS Paris ) -Centre National de la Recherche Scientifique ( CNRS ) -École normale supérieure - Paris ( ENS Paris ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: Cancer Research, MESH : Transcription Factors, PAX3, Regulator genes, [SDV.GEN] Life Sciences [q-bio]/Genetics, MyoD, Muscle Development, 0302 clinical medicine, Molecular Cell Biology, Gene Regulatory Networks, MESH: Animals, MESH : Homeodomain Proteins, Skeletal muscles, Genetics (clinical), MESH: Gene Regulatory Networks, Regulation of gene expression, Genetics, 0303 health sciences, PITX2, Myogenesis, MESH: Transcription Factors, musculoskeletal system, Somites, Regulatory sequence, embryonic structures, MESH: Muscle Development, MYF5, In situ hybridization, Research Article, animal structures, lcsh:QH426-470, MESH : Muscle Development, DNA transcription, Biology, 03 medical and health sciences, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], MESH: Homeodomain Proteins, Animals, Molecular Biology, Ecology, Evolution, Behavior and Systematics, Myogenin, 030304 developmental biology, Homeodomain Proteins, [SDV.GEN]Life Sciences [q-bio]/Genetics, Embryos, Gene regulation, lcsh:Genetics, MESH : Gene Regulatory Networks, MESH : Animals, Gene expression, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, 030217 neurology & neurosurgery, Transcription Factors, Developmental Biology
Abstract: In mammals, several genetic pathways have been characterized that govern engagement of multipotent embryonic progenitors into the myogenic program through the control of the key myogenic regulatory gene Myod. Here we demonstrate the involvement of Six homeoproteins. We first targeted into a Pax3 allele a sequence encoding a negative form of Six4 that binds DNA but cannot interact with essential Eya co-factors. The resulting embryos present hypoplasic skeletal muscles and impaired Myod activation in the trunk in the absence of Myf5/Mrf4. At the axial level, we further show that Myod is still expressed in compound Six1/Six4:Pax3 but not in Six1/Six4:Myf5 triple mutant embryos, demonstrating that Six1/4 participates in the Pax3-Myod genetic pathway. Myod expression and head myogenesis is preserved in Six1/Six4:Myf5 triple mutant embryos, illustrating that upstream regulators of Myod in different embryonic territories are distinct. We show that Myod regulatory regions are directly controlled by Six proteins and that, in the absence of Six1 and Six4, Six2 can compensate., Author Summary The onset of skeletal muscle formation is controlled by complex gene regulatory networks. By manipulation of these genetic pathways in the mouse embryo, we have examined the interplay between genes encoding the transcriptional regulator Pax3; the major myogenic determination proteins Myf5, Mrf4, and Myod; as well as genes encoding homeodomain proteins Six1 and Six4. In the absence of Myf5 and Six1/4, Myod expression is compromised. We demonstrate that key regulatory elements of the Myod gene are directly targeted by Six factors, including Six2, which is unexpectedly upregulated in the absence of Six1 and Six4. This work therefore reveals new aspects of the gene regulatory networks that control myogenesis.
Published: 2013
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7. Single-cell analysis of thymocyte differentiation: identification of transcription factor interactions and a major stochastic component in αβ-lineage commitment

Author: Sophie Ezine, Benedita Rocha, Serge M. Candéias, Amine Boudil, Agnès Legrand, Lamia Skhiri, Laetitia Gautreau-Rolland, Marie Bedora-Faure, Valérie Pasqualetto, Différenciation et physiologie des lymphocytes T (U1020), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Laboratoire de Chimie et Biologie des Métaux (LCBM - UMR 5249), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Laboratoire de Chimie et Biologie des Métaux ( LCBM - UMR 5249 ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Université Paris Descartes - Paris 5 ( UPD5 ), Différenciation et physiologie des lymphocytes T ( U1020 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), and Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG)
Subjects: MESH : Cell Line, MESH : Transcription Factors, Cellular differentiation, lcsh:Medicine, MESH : Thymocytes, Mice, 0302 clinical medicine, Single-cell analysis, Gene expression, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH: Animals, lcsh:Science, 0303 health sciences, Multidisciplinary, Thymocytes, GATA3, Cell Differentiation, MESH: Transcription Factors, medicine.anatomical_structure, MESH : Single-Cell Analysis, MESH: Stochastic Processes, [SDV.IMM]Life Sciences [q-bio]/Immunology, Single-Cell Analysis, MESH : Cell Differentiation, Research Article, MESH: Cell Differentiation, MESH: Thymocytes, T cell, MESH : Cell Lineage, MESH : Stochastic Processes, Biology, Cell Line, 03 medical and health sciences, MESH: Gene Expression Profiling, MESH : Mice, medicine, Animals, Cell Lineage, Transcription factor, MESH: Mice, 030304 developmental biology, Stochastic Processes, MESH : Gene Expression Profiling, Gene Expression Profiling, lcsh:R, MESH: Cell Lineage, Molecular biology, MESH: Cell Line, Gene expression profiling, Cell culture, lcsh:Q, MESH : Animals, 030215 immunology, Transcription Factors, MESH: Single-Cell Analysis
Abstract: International audience; T cell commitment and $\alpha\beta$/$\gamma\delta$ lineage specification in the thymus involves interactions between many different genes. Characterization of these interactions thus requires a multiparameter analysis of individual thymocytes. We developed two efficient single-cell methods: (i) the quantitative evaluation of the co-expression levels of nine different genes, with a plating efficiency of 99-100% and a detection limit of 2 mRNA molecules/cell; and (ii) single-cell differentiation cultures, in the presence of OP9 cells transfected with the thymus Notch1 ligand DeltaL4. We show that during T cell commitment, Gata3 has a fundamental, dose-dependent role in maintaining Notch1 expression, with thymocytes becoming T-cell-committed when they co-express Notch1, Gata3 and Bc11b. Of the transcription factor expression patterns studied here, only that of Bcl11b was suggestive of a role in Pu1 down-regulation. Individual thymocytes became $\alpha\beta$$\gamma\delta$-lineage-committed at very different stages (from the TN2a stage onwards). However, 20% of TN3 cells are not $\alpha\beta$/$\gamma\delta$ lineage committed and TN4 cells comprise two main subpopulations with different degrees of maturity. The existence of a correlation between differentiation potential and expression of the pre-TCR showed that 83% of $\alpha\beta$-committed cells do not express the pre-TCR and revealed a major stochastic component in $\alpha\beta$-lineage specification.
Published: 2013
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8. Genetic polymorphisms in ARID5B, CEBPE, IKZF1 and CDKN2A in relation with risk of acute lymphoblastic leukaemia in adults: a Group for Research on Adult Acute Lymphoblastic Leukaemia (GRAALL) study

Author: Eric Delabesse, Xavier Thomas, Véronique Lhéritier, Nicolas Pottier, Jean-Yves Cahn, Elizabeth Macintyre, Soizic Guihard, Nathalie Grardel, Meyling Cheok, Arnaud Pigneux, Céline Berthon, Hervé Dombret, Norbert Ifrah, Pauline Peyrouze, Marie C. Béné, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Impact de l'environnement chimique sur la santé humaine - ULR 4483 (IMPECS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), TheREx, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Service d'Immunologie [CHRU Nancy], Service hématologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Lymphocyte et cancer, IFR105-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hématologie clinique [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de recherche Jean-Pierre Aubert-Neurosciences et Cancer, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lille, Droit et Santé, Impact de l'Environnement Chimique sur la Santé Humain, PRES Université Lille Nord de France, Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications [Grenoble] ( TIMC-IMAG ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -IMAG-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -IMAG-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Hospices Civils de Lyon ( HCL ), IFR105-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne-Université Paris 13 ( UP13 ), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc - U837 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université Lille 2 - Faculté de Médecine, Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Avicenne
Subjects: Male, MESH : Transcription Factors, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH: CCAAT-Enhancer-Binding Proteins, 0302 clinical medicine, CDKN2A, MESH : Precursor Cell Lymphoblastic Leukemia-Lymphoma, MESH : Female, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, MESH: Middle Aged, MESH: Polymorphism, Single Nucleotide, MESH : Polymorphism, Single Nucleotide, MESH: Genetic Predisposition to Disease, Hematology, MESH: Transcription Factors, MESH: Ikaros Transcription Factor, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma, MESH : Adult, 3. Good health, DNA-Binding Proteins, MESH : CCAAT-Enhancer-Binding Proteins, MESH: Young Adult, 030220 oncology & carcinogenesis, Female, MESH : DNA-Binding Proteins, Adult, MESH : Male, MESH : Young Adult, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Polymorphism, Single Nucleotide, 03 medical and health sciences, Ikaros Transcription Factor, Young Adult, MESH : Ikaros Transcription Factor, Humans, Genetic Predisposition to Disease, MESH : Middle Aged, 030304 developmental biology, MESH: Precursor Cell Lymphoblastic Leukemia-Lymphoma, MESH: Humans, MESH : Humans, MESH: Adult, CEBPE, MESH: Male, Immunology, CCAAT-Enhancer-Binding Proteins, Lymphoblastic leukaemia, MESH : Genetic Predisposition to Disease, MESH: Female, MESH: DNA-Binding Proteins, Transcription Factors
Abstract: International audience
Published: 2012
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9. [The two faces of p63, Janus of the p53 gene family]

Author: Caron De Fromentel, Claude, Aberdam, Edith, Aberdam, Daniel, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris Descartes - Faculté de Médecine ( UPD5 Médecine ), Université Paris Descartes - Paris 5 ( UPD5 ), Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, MESH : Transcription Factors, MESH : Multigene Family, MESH: Genes, p53, MESH : Epidermis, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH : Models, Biological, MESH: Protein Isoforms, MESH : Genes, p53, Models, Biological, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH: Gene Expression Regulation, Developmental, Animals, Humans, Protein Isoforms, MESH: Animals, MESH: Tumor Suppressor Proteins, MESH: Humans, MESH : Tumor Suppressor Proteins, Tumor Suppressor Proteins, MESH : Humans, MESH: Models, Biological, Gene Expression Regulation, Developmental, MESH : Protein Isoforms, MESH: Adult, MESH: Transcription Factors, MESH : Adult, Genes, p53, Multigene Family, MESH: Multigene Family, MESH : Animals, MESH : Gene Expression Regulation, Developmental, Epidermis, MESH: Epidermis, Transcription Factors
Abstract: International audience; The TP53 family member TP63 encodes two main isoforms TAp63 and ΔNp63 with distinct, often opposite functions during development and in the adult. ΔNp63 is crucial for the formation of the ectodermal derivatives and epidermis, while TAp63 is essential for heart development. In the adult, ΔNp63 behaves as a cell survival factor, controlling cell proliferation, adhesion and cell differentiation. In contrast, TAp63 is a proapoptotic factor that protects oocytes from genotoxic insults and prevents premature aging of dermal stem cells. In agreement with these activities, TAp63 is often lost and ΔNp63 overexpressed in cancer cells. Because of their opposite and competitive effects, p63 isoforms could be viewed as Janus two faces. The review focuses on the accumulating data on the p63 functions and regulation in the last decade.
Published: 2012
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10. The glutaredoxin ATGRXS13 is required to facilitate Botrytis cinerea infection of Arabidopsis thaliana plants

Author: La Camera, Sylvain, L'Haridon, Floriane, Astier, Jérémy, Zander, Mark, Abou-Mansour, Eliane, Page, Gonzague, Thurow, Corinna, Wendehenne, David, Gatz, Christiane, Métraux, Jean-Pierre, Lamotte, Olivier, PhyMoTS, Laboratoire de catalyse en chimie organique (LACCO), Centre National de la Recherche Scientifique (CNRS)-Université de Poitiers-Centre National de la Recherche Scientifique (CNRS)-Université de Poitiers, Plante - microbe - environnement : biochimie, biologie cellulaire et écologie (PMEBBCE), Etablissement National d'Enseignement Supérieur Agronomique de Dijon (ENESAD)-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Management et Relations internationales, ESG, Catalyse en chimie organique ( LACCO ), Université de Poitiers-Centre National de la Recherche Scientifique ( CNRS ) -Université de Poitiers-Centre National de la Recherche Scientifique ( CNRS ), Plante - microbe - environnement : biochimie, biologie cellulaire et écologie ( PMEBBCE ), Etablissement National d'Enseignement Supérieur Agronomique de Dijon ( ENESAD ) -Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -Centre National de la Recherche Scientifique ( CNRS ), Equipe Physiologie Moléculaire du Transport de Sucres (PhyMoTS), Université de Poitiers-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Poitiers-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Université de Bourgogne (UB)-Institut National de la Recherche Agronomique (INRA)-Etablissement National d'Enseignement Supérieur Agronomique de Dijon (ENESAD)
Subjects: MESH: Signal Transduction, MESH : Molecular Sequence Data, MESH : Transcription Factors, Arabidopsis, MESH : Alternative Splicing, MESH: Amino Acid Sequence, MESH: RNA, Plant, MESH : Arabidopsis Proteins, necrotrophic pathogen, MESH : Arabidopsis, MESH: Plant Diseases, [ SDV.MP ] Life Sciences [q-bio]/Microbiology and Parasitology, Gene Expression Regulation, Plant, MESH: Arabidopsis, Cloning, Molecular, Disease Resistance, Oligonucleotide Array Sequence Analysis, MESH : Amino Acid Sequence, MESH : Plant Diseases, MESH: Alternative Splicing, MESH : Oxylipins, food and beverages, MESH : Glutaredoxins, MESH: Transcription Factors, MESH : Oligonucleotide Array Sequence Analysis, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, RNA, Plant, MESH: Salicylic Acid, Botrytis, botrytis cinerea, Salicylic Acid, Signal Transduction, MESH : Botrytis, MESH : Cloning, Molecular, MESH: Oxylipins, MESH: Glutaredoxins, Molecular Sequence Data, MESH: Disease Resistance, MESH: Arabidopsis Proteins, Cyclopentanes, MESH: Botrytis, MESH : Disease Resistance, MESH: Cloning, Molecular, Amino Acid Sequence, Oxylipins, MESH: Gene Expression Regulation, Plant, Glutaredoxins, Plant Diseases, MESH : Signal Transduction, MESH : Mutagenesis, Insertional, MESH: Molecular Sequence Data, MESH : RNA, Plant, MESH : Salicylic Acid, Arabidopsis Proteins, jasmonic acid, fungi, glutaredoxin, Alternative Splicing, Mutagenesis, Insertional, MESH: Mutagenesis, Insertional, MESH: Oligonucleotide Array Sequence Analysis, MESH: Cyclopentanes, MESH : Cyclopentanes, MESH : Gene Expression Regulation, Plant, Transcription Factors
Abstract: International audience; Botrytis cinerea is a major pre- and post-harvest necrotrophic pathogen with a broad host range that causes substantial crop losses. The plant hormone jasmonic acid (JA) is involved in the basal resistance against this fungus. Despite basal resistance, virulent strains of B. cinerea can cause disease on Arabidopsis thaliana and virulent pathogens can interfere with the metabolism of the host in a way to facilitate infection of the plant. However, plant genes that are required by the pathogen for infection remain poorly described. To find such genes, we have compared the changes in gene expression induced in A. thaliana by JA with those induced after B. cinerea using genome-wide microarrays. We have identified genes that are repressed by JA but that are induced by B. cinerea. In this study, we describe one candidate gene, ATGRXS13, that encodes for a putative glutaredoxin and that exhibits such a crossed expression. In plants that are infected by this necrotrophic fungus, ATGRXS13 expression was negatively controlled by JA and TGA transcription factors but also through a JA-salicylic acid (SA) cross-talk mechanism as B. cinerea induced SA production that positively controlled ATGRXS13 expression. Furthermore, plants impaired in ATGRXS13 exhibited resistance to B. cinerea. Finally, we present a model whereby B. cinerea takes advantage of defence signalling pathways of the plant to help the colonization of its host.
Published: 2011
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11. Trade-off between bile resistance and nutritional competence drives Escherichia coli diversification in the mouse gut

Author: Nadine Cerf-Bensussan, Dominique Rainteau, François Taddei, Sabine Rakotobe, Marianne De Paepe, Valérie Gaboriau-Routhiau, Interactions de l'épithelium intestinal et du système immunitaire (UMR_S 793), Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Inflammation intestinale, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Robustesse et évolvabilité de la vie (U1001), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), MDP was supported by the Fondation pour la Recherche Médicale (http://www.frm.org/)., Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Recherche Agronomique (INRA), Interactions de l'épithelium intestinal et du système immunitaire ( UMR_S 793 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Recherche Agronomique ( INRA ), MICrobiologie de l'ALImentation au Service de la Santé humaine ( MICALIS ), Institut National de la Recherche Agronomique ( INRA ) -AgroParisTech, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Robustesse et évolvabilité de la vie ( U1001 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), and Autard, Delphine
Subjects: Operon, Mutant, Genetic Fitness, MESH: Escherichia coli Proteins, Mice, MESH : Selection, Genetic, MESH: Animals, 0303 health sciences, MESH : Trans-Activators, MESH: Escherichia coli, Escherichia coli Proteins, Microbiology and Parasitology, Bacterial, SDV:GEN, MESH: Transcription Factors, MESH : Multienzyme Complexes, Microbiologie et Parasitologie, MESH : Phenotype, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Animals, Bacterial Outer Membrane Proteins, Bile Acids and Salts, Biodiversity, DNA-Binding Proteins, Escherichia coli, Flagella, Gastrointestinal Tract, Gene Expression Regulation, Immunity, Innate, Multienzyme Complexes, Mutation, Nutritional Physiological Phenomena, Phenotype, Selection, Genetic, Trans-Activators, Transcription Factors, MESH : DNA-Binding Proteins, MESH : Gene Expression Regulation, Bacterial, MESH: Phenotype, Microbiology, MESH: Flagella, MESH: Biodiversity, 03 medical and health sciences, Genetics, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Molecular Biology, Biology, Ecology, Evolution, Behavior and Systematics, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH : Genetic Fitness, 030306 microbiology, MESH: Bacterial Outer Membrane Proteins, Immunity, Innate, Colonisation, Regulon, MESH : Nutritional Physiological Phenomena, MESH: Gastrointestinal Tract, MESH : Gastrointestinal Tract, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, Cancer Research, MESH : Escherichia coli, MESH : Transcription Factors, MESH: Selection, Genetic, [SDV.GEN] Life Sciences [q-bio]/Genetics, Gut flora, medicine.disease_cause, MESH: Multienzyme Complexes, MESH: Genetic Fitness, [ SDV.MP ] Life Sciences [q-bio]/Microbiology and Parasitology, MESH : Biodiversity, Genetics (clinical), 2. Zero hunger, Experimental evolution, MESH: Gene Expression Regulation, Bacterial, biology, MESH : Escherichia coli Proteins, MESH : Immunity, Innate, MESH: Immunity, Innate, MESH : Mutation, Research Article, MESH: Mutation, lcsh:QH426-470, MESH: Trans-Activators, MESH: Bile Acids and Salts, Model Organisms, MESH : Mice, medicine, Selection, Genetic, MESH: Nutritional Physiological Phenomena, MESH : Bacterial Outer Membrane Proteins, MESH: Mice, 030304 developmental biology, Evolutionary Biology, Gene Expression Regulation, Bacterial, biology.organism_classification, MESH : Bile Acids and Salts, lcsh:Genetics, bacteria, MESH : Animals, MESH : Flagella, MESH: DNA-Binding Proteins
Abstract: Bacterial diversification is often observed, but underlying mechanisms are difficult to disentangle and remain generally unknown. Moreover, controlled diversification experiments in ecologically relevant environments are lacking. We studied bacterial diversification in the mammalian gut, one of the most complex bacterial environments, where usually hundreds of species and thousands of bacterial strains stably coexist. Herein we show rapid genetic diversification of an Escherichia coli strain upon colonisation of previously germ-free mice. In addition to the previously described mutations in the EnvZ/OmpR operon, we describe the rapid and systematic selection of mutations in the flagellar flhDC operon and in malT, the transcriptional activator of the maltose regulon. Moreover, within each mouse, the three mutant types coexisted at different levels after one month of colonisation. By combining in vivo studies and determination of the fitness advantages of the selected mutations in controlled in vitro experiments, we provide evidence that the selective forces that drive E. coli diversification in the mouse gut are the presence of bile salts and competition for nutrients. Altogether our results indicate that a trade-off between stress resistance and nutritional competence generates sympatric diversification of the gut microbiota. These results illustrate how experimental evolution in natural environments enables identification of both the selective pressures that organisms face in their natural environment and the diversification mechanisms., Author Summary The mechanisms generating the huge biodiversity on earth are not entirely understood. Bacterial populations are powerful models to explore the mechanisms of evolution, owing to their big population size, rapid growth, and high mutation rate. One of the more complex bacterial community is the mammalian gut microbiota, and Escherichia coli is one of the first colonizers of the newborn intestine. Herein we studied diversification of an Escherichia coli strain in germ-free mice, a simplified though ecologically relevant system. We show rapid genetic diversification upon colonization, characterized by the systematic selection of mutations in three different pathways: in the global regulator EnvZ/OmpR controlling outer membrane permeability, in the flagellar operon, and in the maltose regulon. By combining in vivo and in vitro experiments, we show that the selective forces that drive E. coli diversification are the presence of bile salts and the competition for nutrients. Altogether our results indicate that a trade-off between stress resistance and nutritional competence is sufficient to mediate diversification of bacteria. These results illustrate how experimental evolution in natural environments allows the identification of the selective pressures that organisms face in their natural environment, as well as the diversification mechanisms.
Published: 2011
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12. Pituitary stalk interruption syndrome in 83 patients: novel HESX1 mutation and severe hormonal prognosis in malformative forms

Author: Raja Brauner, Jean Gaudart, Gilbert Simonin, Thierry Brue, Emilie Carmona, Frédérique Albarel, Anne Barlier, Nourredine Kaffel, Frederic Castinetti, Alain Enjalbert, P. Lecomte, Alexandru Saveanu, Rachel Reynaud, Centre de recherche en neurobiologie - neurophysiologie de Marseille (CRN2M), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5), Méthodes Algorithmes pour l'Ordonnancement et les Réseaux (MAORE), Laboratoire d'Informatique de Robotique et de Microélectronique de Montpellier (LIRMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Laboratoire d'Enseignement et de Recherche sur le Traitement de l'Information Médicale (LERTIM), Université de la Méditerranée - Aix-Marseille 2, Centre de recherche en neurobiologie - neurophysiologie de Marseille ( CRN2M ), Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris Descartes - Paris 5 ( UPD5 ), Méthodes Algorithmes pour l'Ordonnancement et les Réseaux ( MAORE ), Laboratoire d'Informatique de Robotique et de Microélectronique de Montpellier ( LIRMM ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire d'Enseignement et de Recherche sur le Traitement de l'Information Médicale ( LERTIM ), Methods, Algorithms for Operations REsearch (MAORE), and Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, MESH : Transcription Factors, Endocrinology, Diabetes and Metabolism, Pedigree chart, Hypopituitarism, MESH : Child, Preschool, medicine.disease_cause, MESH : Pituitary Gland, MESH: Magnetic Resonance Imaging, 0302 clinical medicine, Endocrinology, [ SDV.BBM.BC ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], MESH : Child, MESH: Otx Transcription Factors, MESH: Pituitary Gland, MESH: SOXB1 Transcription Factors, MESH: Child, MESH : Female, MESH : Homeodomain Proteins, Child, 0303 health sciences, education.field_of_study, Mutation, Otx Transcription Factors, MESH : Otx Transcription Factors, MESH : SOXB1 Transcription Factors, Incidence (epidemiology), MESH : Infant, General Medicine, MESH: Transcription Factors, Magnetic Resonance Imaging, MESH: Infant, Ectopic Posterior Pituitary, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], medicine.anatomical_structure, Child, Preschool, Pituitary Gland, Cohort, Female, MESH : Mutation, medicine.medical_specialty, MESH: Mutation, Adolescent, MESH : Male, LIM-Homeodomain Proteins, Population, 030209 endocrinology & metabolism, Biology, 03 medical and health sciences, Posterior pituitary, Internal medicine, MESH : Adolescent, MESH : Magnetic Resonance Imaging, MESH: Homeodomain Proteins, medicine, Humans, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], education, 030304 developmental biology, Homeodomain Proteins, MESH: Adolescent, MESH: Humans, SOXB1 Transcription Factors, MESH : Humans, MESH: Child, Preschool, Infant, medicine.disease, MESH: Male, MESH: Female, Transcription Factors
Abstract: BackgroundPituitary stalk interruption syndrome (PSIS) is a particular entity in the population of patients with hypopituitarism. Only rare cases have a known genetic cause.Objectivesi) To compare subgroups with or without extra-pituitary malformations (EPM) in a cohort of PSIS patients to identify predictive factors of evolution, ii) to determine the incidence of mutations of the known pituitary transcription factor genes in PSIS.Study designWe analyzed features of 83 PSIS patients from 80 pedigrees and screened HESX1, LHX4, OTX2, and SOX3 genes.ResultsPSIS had a male predominance and was rarely familial (5%). Pituitary hypoplasia was observed only in the group with EPM. Multiple hormone deficits were observed significantly more often with versus without EPM (87.5 vs 69.5% respectively). Posterior pituitary location along the stalk was a significant protective factor regarding severity of hormonal phenotype. A novel HESX1 causative mutation was found in a consanguineous family, and two LHX4 mutations were present in familial PSIS.ConclusionPSIS patients with EPM had a more severe hormonal disorder and pituitary imaging status, suggesting an antenatal origin. HESX1 or LHX4 mutations accounted for
Published: 2011
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13. Effects of typical inducers on olfactory xenobiotic-metabolizing enzyme, transporter, and transcription factor expression in rats

Author: Joëlle Chevalier, Yves Artur, Jean-Marie Heydel, Anne-Marie Le Bon, Maud Sigoillot, Nicolas Thiebaud, Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB), Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), and Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS )
Subjects: Male, LIVER, MESH : Transcription Factors, MESH: Microsomes, Liver, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, Pharmaceutical Science, MESH : Cytochromes, MESH: Down-Regulation, MESH: Membrane Transport Proteins, MESH : Down-Regulation, Cytosol, 0302 clinical medicine, Glucocorticoid receptor, MESH : Membrane Transport Proteins, MESH: Cytosol, MESH: Reverse Transcriptase Polymerase Chain Reaction, Gene expression, Constitutive androstane receptor, MESH: Up-Regulation, MESH: Animals, Receptor, MESH : Up-Regulation, MESH: Cytochromes, 0303 health sciences, Pregnane X receptor, MESH : Metabolic Detoxication, Phase I, biology, Reverse Transcriptase Polymerase Chain Reaction, MESH : Rats, MESH : Cytosol, INDUCTION, MESH : Reverse Transcriptase Polymerase Chain Reaction, MESH: Transcription Factors, Up-Regulation, 3. Good health, MESH : Microsomes, Liver, HYDROCARBON HYDROXYLASE-ACTIVITY, medicine.anatomical_structure, PHASE-I, Biochemistry, MESH: Metabolic Detoxication, Phase II, Enzyme Induction, Microsomes, Liver, MESH: Metabolic Detoxication, Phase I, MESH: Xenobiotics, MESH: Enzyme Induction, MESH: Rats, MESH : Male, Down-Regulation, MESH : Xenobiotics, PHENOL SULFOTRANSFERASE, MESH : Rats, Wistar, Xenobiotics, 03 medical and health sciences, Olfactory mucosa, Olfactory Mucosa, medicine, Animals, Rats, Wistar, MESH: Olfactory Mucosa, Transcription factor, 030304 developmental biology, Pharmacology, MESH : Olfactory Mucosa, IDENTIFICATION, RECEPTOR, MESH : Enzyme Induction, Membrane Transport Proteins, MESH : Metabolic Detoxication, Phase II, UDP-GLUCURONOSYLTRANSFERASE, MESH: Rats, Wistar, Aryl hydrocarbon receptor, ORGANIC ANION TRANSPORTER, Molecular biology, Metabolic Detoxication, Phase II, MESH: Male, Rats, NASAL-MUCOSA, biology.protein, Cytochromes, Metabolic Detoxication, Phase I, MESH : Animals, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, 030217 neurology & neurosurgery, Transcription Factors
Abstract: International audience; Several xenobiotic-metabolizing enzymes (XMEs) have been identified in the olfactory mucosa (OM) of mammals. However, the molecular mechanisms underlying the regulation of these enzymes have been little explored. In particular, information on the expression of the transcriptional factors in this tissue is quite limited. The aim of the present study was to examine the impact of five typical inducers, Aroclor 1254, 3-methylcholanthrene, dexamethasone, phenobarbital, and ethoxyquin, on the activities and mRNA expression of several XMEs in the OM and in the liver of rats. We also evaluated the effects of these treatments on the mRNA expression of transcription factors and transporters. On the whole, the intensities of the effects were lower in the OM than in the liver. Dexamethasone was found to be the most efficient treatment in the OM. Dexamethasone induced the transcription of several olfactory phase I, II, and III genes [such as cytochromes P450 2A3 and 3A9, UDP-glucuronosyltransferase (UGT) 2A1, and multidrug resistance-related protein type 1] and increased UGT activities. We observed that dexamethasone up-regulated sulfotransferase 1C1 expression in the OM but down-regulated it in the liver. Aroclor and ethoxyquin induced the gene expression of CYP1A and quinone reductase, respectively, in the OM. The transcription factors aryl hydrocarbon receptor, nuclear factor E2-related factor 2 (Nrf2), peroxisome proliferator-activated receptor α, pregnane X receptor, and glucocorticoid receptor were detected in the OM, but no constitutive androstane receptor expression was observed. Dexamethasone and Aroclor enhanced olfactory Nrf2 expression. These results demonstrate that olfactory XME can be modulated by chemicals and that the mechanisms involved in the regulation of these enzymes are tissue-specific.
Published: 2010
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14. Dlx homeobox gene family expression in osteoclasts

Author: Dominique Heymann, Frédéric Lézot, Alba Bolaños, Beatriz Castaneda, D. Hotton, Ariane Berdal, Bethan Thomas, Agamemnon E. Grigoriadis, G.F. Carles, Claudine Blin-Wakkach, Paul T. Sharpe, Centre de Recherche des Cordeliers ( CRC (UMR_S 872) ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Génétique, physiopathologie et ingénierie du tissu osseux ( GéPITOS ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Université de Nantes ( UN ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique, physiopathologie et ingénierie du tissu osseux (GéPITOS), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Nice Sophia Antipolis (1965 - 2019) (UNS), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), and Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, MESH : Cell Line, MESH : Transcription Factors, Physiology, Cellular differentiation, Clinical Biochemistry, Osteoclasts, Mandible, Mice, 0302 clinical medicine, MESH : Acid Phosphatase, Osteogenesis, MESH: Osteoclasts, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH: Gene Expression Regulation, Developmental, MESH : Osteogenesis, MESH: Animals, MESH : Homeodomain Proteins, MESH : Matrix Metalloproteinase 9, MESH: Osteogenesis, Tartrate-resistant acid phosphatase, Regulation of gene expression, MESH : Isoenzymes, 0303 health sciences, Reverse Transcriptase Polymerase Chain Reaction, DLX2, MESH : Reverse Transcriptase Polymerase Chain Reaction, Gene Expression Regulation, Developmental, Cell Differentiation, MESH: Transcription Factors, DLX6, MESH : beta-Galactosidase, DLX5, Isoenzymes, MESH: beta-Galactosidase, Matrix Metalloproteinase 9, Multigene Family, 030220 oncology & carcinogenesis, MESH: Isoenzymes, MESH : Cell Differentiation, MESH: Cell Differentiation, musculoskeletal diseases, MESH : Mandible, MESH : Male, Acid Phosphatase, MESH : Multigene Family, MESH: Mandible, Biology, Cell Line, MESH: Acid Phosphatase, MESH: Gene Expression Profiling, 03 medical and health sciences, MESH: Homeodomain Proteins, MESH : Mice, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Mice, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, Homeodomain Proteins, Tartrate-Resistant Acid Phosphatase, Gene Expression Profiling, MESH : Gene Expression Profiling, MESH: Matrix Metalloproteinase 9, Cell Biology, beta-Galactosidase, Molecular biology, MESH: Male, MESH: Cell Line, Gene expression profiling, MESH : Osteoclasts, MESH: Multigene Family, Homeobox, MESH : Animals, MESH : Gene Expression Regulation, Developmental, Transcription Factors
Abstract: International audience; Skeletal growth and homeostasis require the finely orchestrated secretion of mineralized tissue matrices by highly specialized cells, balanced with their degradation by osteoclasts. Time- and site-specific expression of Dlx and Msx homeobox genes in the cells secreting these matrices have been identified as important elements in the regulation of skeletal morphology. Such specific expression patterns have also been reported in osteoclasts for Msx genes. The aim of the present study was to establish the expression patterns of Dlx genes in osteoclasts and identify their function in regulating skeletal morphology. The expression patterns of all Dlx genes were examined during the whole osteoclastogenesis using different in vitro models. The results revealed that Dlx1 and Dlx2 are the only Dlx family members with a possible function in osteoclastogenesis as well as in mature osteoclasts. Dlx5 and Dlx6 were detected in the cultures but appear to be markers of monocytes and their derivatives. In vivo, Dlx2 expression in osteoclasts was examined using a Dlx2/LacZ transgenic mouse. Dlx2 is expressed in a subpopulation of osteoclasts in association with tooth, brain, nerve, and bone marrow volumetric growths. Altogether the present data suggest a role for Dlx2 in regulation of skeletal morphogenesis via functions within osteoclasts.
Published: 2010
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15. A follow-up study of a genome-wide association scan identifies a susceptibility locus for venous thrombosis on chromosome 6p24.1

Author: Marie-Christine Alessi, Mark Lathrop, Simon Heath, Diana Zelenika, Jessy Brocheton, Jean-François Schved, Marine Germain, Pilar Galan, Ewa Ninio, Stefan Blankenberg, Thomas Münzel, Joseph Emmerich, Irene D. Bezemer, Christine Biron-Andreani, François Cambien, Aurélien Delluc, Noémie Saut, Tanja Zeller, David-Alexandre Trégouët, Ludovic Drouet, Frits R. Rosendaal, Laurence Tiret, Pierre-Emmanuel Morange, Viviane Nicaud, Hervé Durand, Stefan-Martin Brand-Herrmann, Gwenaelle Burgos, Lance A. Bare, Gilles Pernod, Nutrition, obésité et risque thrombotique (NORT), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génomique cardiovasculaire, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique épidémiologique et moléculaire des pathologies cardiovasculaires, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'hématologie biologique[Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi, Techniques pour l'Evaluation et la Modélisation des Actions de la Santé (TIMC-IMAG-ThEMAS), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Unité de Recherche en Epidémiologie Nutritionnelle (UREN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Cité (USPC)-Université Paris 13 (UP13)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut National de la Recherche Agronomique (INRA), Service de Biochimie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-IFR6, Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Département de Médecine Interne et Pneumologie [Brest] (DMIP - Brest), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Department of Medicine II, Johannes Gutenberg - Universität Mainz (JGU), Hôpital de la Timone [CHU - APHM] (TIMONE), Institut de Génomique d'Evry (IG), Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Department of General and Interventional Cardiology, University Heart Center Hamburg, Risque Thrombotique et Mecanismes de l'Hemostase (U765), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Risque Thrombotique et Mécanismes de l'Hémostase (U765), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition, obésité et risque thrombotique ( NORT ), Institut National de la Recherche Agronomique ( INRA ) -Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -IFR14-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Montpellier 1 ( UM1 ) -Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -CHU Saint-Eloi, ThEMAS, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications [Grenoble] ( TIMC-IMAG ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -IMAG-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -IMAG-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Unité de Recherche en Epidémiologie Nutritionnelle ( UREN ), Université Paris 13 ( UP13 ) -Institut National de la Recherche Agronomique ( INRA ) -Conservatoire National des Arts et Métiers [CNAM] ( CNAM ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Lariboisière-IFR6, Centre National de Génotypage ( CNG ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Département de Médecine Interne et Pneumologie [Brest] ( DMIP - Brest ), Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Groupe d'Etude de la Thrombose de Bretagne Occidentale ( GETBO ), Université de Brest ( UBO ), Johannes Gutenberg-University Mainz, Hôpital de la Timone [CHU - APHM] ( TIMONE ), Institut de Génomique d'Evry ( IG ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay, Risque Thrombotique et Mecanismes de l'Hemostase ( U765 ), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement ( IFR71 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-IFR6, Université de Brest (UBO), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)
Subjects: MESH : Transcription Factors, [SDV]Life Sciences [q-bio], Genome-wide association study, 030204 cardiovascular system & hematology, MESH : Chromosomes, Human, Pair 6, 0302 clinical medicine, Genetics(clinical), Genetics (clinical), Genetics, Venous Thrombosis, 0303 health sciences, MESH: Polymorphism, Single Nucleotide, MESH : Polymorphism, Single Nucleotide, MESH: Genetic Predisposition to Disease, MESH: Follow-Up Studies, MESH: Transcription Factors, MESH : Venous Thrombosis, MESH: Case-Control Studies, DNA-Binding Proteins, Chromosomes, Human, Pair 6, MESH : DNA-Binding Proteins, Erratum, MESH : Genome-Wide Association Study, MESH : Case-Control Studies, MESH: Chromosomes, Human, Pair 6, Locus (genetics), Biology, Polymorphism, Single Nucleotide, Genetic determinism, 03 medical and health sciences, Report, Genetic predisposition, Humans, Genetic Predisposition to Disease, Allele, Gene, 030304 developmental biology, MESH: Humans, [ SDV ] Life Sciences [q-bio], MESH : Humans, linking inflammation protein atherothrombosis sequence risk, Case-control study, Chromosome, MESH : Follow-Up Studies, Case-Control Studies, MESH: Genome-Wide Association Study, MESH: Venous Thrombosis, MESH : Genetic Predisposition to Disease, 030217 neurology & neurosurgery, MESH: DNA-Binding Proteins, Follow-Up Studies, Genome-Wide Association Study, Transcription Factors
Abstract: International audience; To identify genetic susceptibility factors conferring increased risk of venous thrombosis (VT), we conducted a multistage study, following results of a previously published GWAS that failed to detect loci for developing VT. Using a collection of 5862 cases with VT and 7112 healthy controls, we identified the HIVEP1 locus on chromosome 6p24.1 as a susceptibility locus for VT. Indeed, the HIVEP1 rs169713C allele was associated with an increased risk for VT, with an odds ratio of 1.20 (95% confidence interval 1.13-1.27, p = 2.86 x 10(-9)). HIVEP1 codes for a protein that participates in the transcriptional regulation of inflammatory target genes by binding specific DNA sequences in their promoter and enhancer regions. The current results provide the identification of a locus involved in VT susceptibility that lies outside the traditional coagulation/fibrinolysis pathway.
Published: 2010
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16. The SNAIL family member SCRATCH1 is not expressed in human tumors

Author: Benjamin Pierre Bouchet, Gaël Grelier, Carole Audoynaud, Stéphane Ansieau, Alain Puisieux, Jérémy Bastid, Claire Ciancia, Julie Pourchet, Oncogénèse et progression tumorale, Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon, equipe 2, Centre Léon Bérard [Lyon]-Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Léon Bérard [Lyon], Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Léon Bérard [Lyon]-Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL )
Subjects: MESH: Carcinoma, Cancer Research, Pathology, MESH : Transcription Factors, Snail, medicine.disease_cause, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Mice, MESH: Mammary Neoplasms, Animal, 0302 clinical medicine, Neoplasms, MESH : Female, MESH: Animals, MESH: Neoplasms, Melanoma, 0303 health sciences, biology, MESH : Carcinoma, General Medicine, MESH: Gene Expression Regulation, Neoplastic, MESH: Transcription Factors, 3. Good health, Gene Expression Regulation, Neoplastic, Oncology, 030220 oncology & carcinogenesis, Female, medicine.medical_specialty, MESH : Gene Expression Regulation, Neoplastic, Slug, MESH: Melanoma, MESH : Mammary Neoplasms, Animal, MESH : Melanoma, Mammary Neoplasms, Animal, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, biology.animal, MESH : Mice, medicine, Animals, Humans, Epithelial–mesenchymal transition, Transcription factor, MESH: Mice, 030304 developmental biology, MESH: Humans, Oncogene, MESH : Humans, Carcinoma, fungi, biology.organism_classification, MESH : Neoplasms, SNAI2, SNAI1, Cancer research, MESH : Animals, Snail Family Transcription Factors, Carcinogenesis, MESH: Female, Transcription Factors
Abstract: International audience; The SNAIL and SLUG transcription factors play important roles in embryogenesis owing to their anti-apoptotic properties and their ability to promote morphogenetic changes by inducing epithelial-mesenchymal transitions (EMT). These characteristics provide many of the proteins in these families with oncogenic and pro-metastatic capabilities when reactivated in cancers. The SCRATCH subgroup of the SNAIL superfamily, including SCRATCH1 and SCRATCH2, display distinct embryonic functions and diverge early in evolution. Despite the described overexpression of SCRT1 (encoding for SCRATCH1) in a small subset of human lung cancers, there is little data supporting a role of SCRATCH proteins in tumorigenesis. To further explore this possibility, we assessed SNAI1 (SNAIL), SNAI2 (SLUG) and SCRT1 (SCRATCH1) expression in a wide panel of human and murine tumors encompassing 151 primary tumors and 6 different cancer types, including melanomas and multiple different carcinomas. Whereas SNAI1 and SNAI2 are widely expressed in human and murine tumors, our results reveal that SCRT1 transcripts are undetectable in nearly all of the examined tumors suggesting that SCRATCH1 plays a minor role, if any, in tumorigenesis. Our data therefore suggest that oncogenic properties are not shared by all SNAIL superfamily members but instead are specifically allotted to the SNAIL subgroup supporting the conclusions that SNAIL and SCRATCH subgroups are functionally divergent and strengthening the hypothesis that the oncogenic potential of SNAIL and SLUG proteins relies on the hijacking of their embryonic functions.
Published: 2010

17. Expression profiling of prospero in the Drosophila larval chemosensory organ: Between growth and outgrowth

Author: Laure Guenin, Mahatsangy Raharijaona, Rémi Houlgatte, Fawzia Baba-Aissa, Pathogénomique mycobactérienne intégrée, Institut Pasteur [Paris], Développement et Communication Chimique chez les Insectes (DCCI), Centre National de la Recherche Scientifique (CNRS)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Institut du thorax, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was funded by the Burgundy Regional Council and the Centre National de la Recherche Scientifique., Développement et Communication Chimique chez les Insectes ( DCCI ), Centre National de la Recherche Scientifique ( CNRS ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Université de Nantes ( UN ) -IFR26-Institut National de la Santé et de la Recherche Médicale ( INSERM ), BMC, Ed., Institut Pasteur [Paris] (IP), and Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Central Nervous System, MESH : Transcription Factors, MESH: Drosophila, OF-FUNCTION SCREEN, MUSCA-DOMESTICA L, HOUSE-FLY LARVA, FINE-STRUCTURE, AXON GUIDANCE, TRANSCRIPTION FACTOR, PATTERN-FORMATION, GENETIC-ANALYSIS, NERVOUS-SYSTEM, Genes, Insect, MESH: Genes, Insect, 0302 clinical medicine, MESH: Gene Expression Regulation, Developmental, Cluster Analysis, Drosophila Proteins, MESH: Animals, MESH: Nerve Tissue Proteins, MESH : Nerve Tissue Proteins, Oligonucleotide Array Sequence Analysis, Genetics, 0303 health sciences, MESH : Central Nervous System, Microbiology and Parasitology, MESH : Genes, Insect, Gene Expression Regulation, Developmental, Nuclear Proteins, MESH: Transcription Factors, Null allele, Microbiologie et Parasitologie, MESH : Oligonucleotide Array Sequence Analysis, [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Larva, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Drosophila, Drosophila Protein, Research Article, Biotechnology, lcsh:QH426-470, MESH: Drosophila Proteins, lcsh:Biotechnology, Nerve Tissue Proteins, Biotechnologies, Biology, 03 medical and health sciences, MESH: Gene Expression Profiling, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], lcsh:TP248.13-248.65, Animals, MESH : Cluster Analysis, MESH: Central Nervous System, Allele, MESH : Drosophila, Alleles, 030304 developmental biology, MESH : Larva, Microarray analysis techniques, Gene Expression Profiling, MESH : Gene Expression Profiling, MESH: Alleles, Wild type, MESH : Nuclear Proteins, Prospero, biology.organism_classification, MESH : Drosophila Proteins, MESH: Cluster Analysis, Gene expression profiling, lcsh:Genetics, MESH: Oligonucleotide Array Sequence Analysis, Homeobox, MESH : Animals, MESH : Gene Expression Regulation, Developmental, MESH : Alleles, MESH: Nuclear Proteins, MESH: Larva, 030217 neurology & neurosurgery, Transcription Factors
Abstract: BackgroundThe antenno-maxilary complex (AMC) forms the chemosensory system of theDrosophilalarva and is involved in gustatory and olfactory perception. We have previously shown that a mutant allele of the homeodomain transcription factor Prospero (prosVoila1,V1), presents several developmental defects including abnormal growth and altered taste responses. In addition, many neural tracts connecting the AMC to the central nervous system (CNS) were affected. Our earlier reports on larval AMC did not argue in favour of a role ofprosin cell fate decision, but strongly suggested thatproscould be involved in the control of other aspect of neuronal development. In order to identify these functions, we used microarray analysis of larval AMC and CNS tissue isolated from the wild type, and three other previously characterisedprosperoalleles, including theV1mutant, considered as a null allele for the AMC.ResultsA total of 17 samples were first analysed with hierarchical clustering. To determine those genes affected by loss ofprosfunction, we calculated a discriminating score reflecting the differential expression betweenV1mutant and otherprosalleles. We identified a total of 64 genes in the AMC. Additional manual annotation using all the computed information on the attributed role of these genes in theDrosophilalarvae nervous system, enabled us to identify one functional category of potential Prospero target genes known to be involved in neurite outgrowth, synaptic transmission and more specifically in neuronal connectivity remodelling. The second category of genes found to be differentially expressed between the null mutant AMC and the other alleles concerned the development of the sensory organs and more particularly the larval olfactory system. Surprisingly, a third category emerged from our analyses and suggests an association ofproswith the genes that regulate autophagy, growth and insulin pathways. Interestingly, EGFR and Notch pathways were represented in all of these three functional categories. We now propose that Pros could perform all of these different functions through the modulation of these two antagonistic and synergic pathways.ConclusionsThe current data contribute to the clarification of theprosperofunction in the larval AMC and show thatprosregulates different function in larvae as compared to those controlled by this gene in embryos. In the future, the possible mechanism by which Pros could achieve its function in the AMC will be explored in detail.
Published: 2010
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18. PHOX2B in respiratory control: lessons from congenital central hypoventilation syndrome and its mouse models

Author: Jorge Gallego, Jeanne Amiel, Nelina Ramanantsoa, Véronique Dubreuil, Christo Goridis, Gilles Fortin, Jean-François Brunet, Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (Inserm U781), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Génétique Médicale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Développement et évolution du système nerveux (DESN), École normale supérieure - Paris (ENS Paris)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie, conséquences fonctionnelles et neuroprotection des atteintes du cerveau en développement, Université Paris Diderot - Paris 7 (UPD7)-IFR2-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Neurobiologie Alfred Fessard (INAF), Centre National de la Recherche Scientifique (CNRS), Neurobiologie génétique et intégrative (NGI), Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement ( Inserm U781 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP), Développement et évolution du système nerveux ( DESN ), École normale supérieure - Paris ( ENS Paris ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris Diderot - Paris 7 ( UPD7 ) -IFR2-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de Neurobiologie Alfred Fessard ( INAF ), Centre National de la Recherche Scientifique ( CNRS ), Neurobiologie génétique et intégrative ( NGI ), and Université Paris Diderot - Paris 7 ( UPD7 )
Subjects: MESH : Oxygen, MESH : Transcription Factors, Physiology, MESH: Carbon Dioxide, MESH: Animals, Newborn, Mice, MESH: Respiratory Center, 0302 clinical medicine, MESH: Animals, MESH : Homeodomain Proteins, Respiratory system, MESH : Temperature, 0303 health sciences, MESH : Chemoreceptor Cells, MESH : Peptides, MESH : Respiratory Center, MESH: Peptides, MESH : Animals, Newborn, Respiration, General Neuroscience, MESH: Infant, Newborn, MESH : Autonomic Nervous System Diseases, Temperature, Sleep apnea, MESH : Infant, MESH: Transcription Factors, Sleep Apnea, Central, MESH: Autonomic Nervous System Diseases, MESH: Infant, Chemoreceptor Cells, MESH: Temperature, Hypoventilation, MESH : Carbon Dioxide, Breathing, MESH : Sleep Apnea, Central, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH : Mutation, medicine.symptom, Hypercapnia, MESH: Oxygen, Pulmonary and Respiratory Medicine, medicine.medical_specialty, MESH: Mutation, MESH: Chemoreceptor Cells, Congenital central hypoventilation syndrome, MESH : Infant, Newborn, 03 medical and health sciences, Internal medicine, MESH : Mice, Parafacial, MESH: Homeodomain Proteins, medicine, Animals, Humans, MESH: Mice, 030304 developmental biology, Homeodomain Proteins, MESH: Respiration, MESH: Humans, business.industry, MESH : Humans, Infant, Newborn, Infant, Carbon Dioxide, Respiratory Center, medicine.disease, MESH : Disease Models, Animal, MESH : Respiration, Oxygen, Disease Models, Animal, Endocrinology, Animals, Newborn, Autonomic Nervous System Diseases, Control of respiration, [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH: Sleep Apnea, Central, Mutation, MESH : Animals, MESH: Disease Models, Animal, Peptides, business, Neuroscience, 030217 neurology & neurosurgery, Transcription Factors
Abstract: International audience; Phox2b is a master regulator of visceral reflex circuits. Its role in the control of respiration has been highlighted by the identification of heterozygous PHOX2B mutations as the cause of Central Congenital Hypoventilation Syndrome (CCHS), a rare disease defined by the lack of CO(2) responsiveness and of breathing automaticity in sleep. Phox2b(27Ala/+) mice that bear a frequent CCHS-causing mutation do not respond to hypercapnia and die in the first hour after birth from central apnoea. They are therefore a reliable animal model for CCHS. Neurons of the retrotrapezoïd nucleus/parafacial respiratory group (RTN/pFRG) were found severely depleted in these mice and no other neuronal loss could be identified. Physiological experiments show that RTN/pFRG neurons are crucial to driving proper breathing at birth and are necessary for central chemoreception and the generation of a normal respiratory rhythm. To date, the reason for the selective vulnerability of RTN/pFRG neurons to PHOX2B protein dysfunction remains unexplained.
Published: 2009
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19. iNKT cell development is orchestrated by different branches of TGF-beta signaling

Author: Sylvie Martel, C Garcia, Régine Losson, Jean-Marc Doisne, Farhan S. Cyprian, Nadia Duarte, Kamel Benlagha, Kai-Ping Yan, Jean-Benoît Le Luduec, Laurent Bartholin, Julien C. Marie, Branka Horvat, David F. Vincent, Ruth Rimokh, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunologie, génétique et traitement des maladies métaboliques et du diabète (UMR_S 561), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Oncogénèse et progression tumorale, Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Louis Pasteur - Strasbourg I, Virologie humaine, École normale supérieure - Lyon (ENS Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunité infection vaccination (I2V), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure de Lyon (ENS de Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Cochin [AP-HP], Immunologie, génétique et traitement des maladies métaboliques et du diabète ( UMR_S 561 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de génétique et biologie moléculaire et cellulaire ( IGBMC ), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), École normale supérieure - Lyon ( ENS Lyon ) -IFR128-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Immunité infection vaccination ( I2V ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-IFR128-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de biologie et chimie des protéines [Lyon] ( IBCP ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), and Peney, Maité
Subjects: MESH: Signal Transduction, MESH : Transcription Factors, MESH : Receptors, Transforming Growth Factor beta, MESH: Spleen, Cellular differentiation, Apoptosis, MESH: T-Lymphocyte Subsets, Mice, 0302 clinical medicine, T-Lymphocyte Subsets, Transforming Growth Factor beta, MESH: Smad4 Protein, Immunology and Allergy, MESH: Animals, Smad4 Protein, 0303 health sciences, biology, Stem Cells, Cell Differentiation, MESH: Transcription Factors, Natural killer T cell, MESH : Mice, Transgenic, Cell biology, MESH: Interleukin-2 Receptor beta Subunit, MESH : Stem Cells, MESH: Receptors, Transforming Growth Factor beta, Stem cell, Signal transduction, MESH : Cell Differentiation, Signal Transduction, MESH : Spleen, MESH: Cell Differentiation, MESH: T-Box Domain Proteins, MESH: Mice, Transgenic, Immunology, MESH : Cell Lineage, Mice, Transgenic, MESH: Stem Cells, Article, 03 medical and health sciences, MESH : Mice, TGF beta signaling pathway, Animals, Cell Lineage, Transcription factor, MESH: Mice, MESH: Transforming Growth Factor beta, MESH : Interleukin-2 Receptor beta Subunit, 030304 developmental biology, MESH : Signal Transduction, Cell growth, MESH: Apoptosis, MESH : Smad4 Protein, Transforming growth factor beta, MESH: Cell Lineage, MESH : Natural Killer T-Cells, MESH : T-Lymphocyte Subsets, Interleukin-2 Receptor beta Subunit, MESH : T-Box Domain Proteins, MESH : Transforming Growth Factor beta, MESH: Natural Killer T-Cells, biology.protein, Natural Killer T-Cells, MESH : Animals, T-Box Domain Proteins, Receptors, Transforming Growth Factor beta, Spleen, MESH : Apoptosis, Transcription Factors, 030215 immunology
Abstract: International audience; Invariant natural killer T (iNKT) cells constitute a distinct subset of T lymphocytes exhibiting important immune-regulatory functions. Although various steps of their differentiation have been well characterized, the factors controlling their development remain poorly documented. Here, we show that TGF-beta controls the differentiation program of iNKT cells. We demonstrate that TGF-beta signaling carefully and specifically orchestrates several steps of iNKT cell development. In vivo, this multifaceted role of TGF-beta involves the concerted action of different pathways of TGF-beta signaling. Whereas the Tif-1gamma branch controls lineage expansion, the Smad4 branch maintains the maturation stage that is initially repressed by a Tif-1gamma/Smad4-independent branch. Thus, these three different branches of TGF-beta signaling function in concert as complementary effectors, allowing TGF-beta to fine tune the iNKT cell differentiation program.
Published: 2009
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20. Erk5 controls Slug expression and keratinocyte activation during wound healing

Author: Pierre Savagner, Valérie Arnoux, Annie L'Helgoualc'h, Mayssaa Nassour, Robert A. Hipskind, Genotypes et Phenotypes Tumoraux, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Ligue Regionale contre le Cancer (Languedoc-Roussillon), Groupement des Entreprises Francaises dans la Lutte contre le Cancer, the Fondation de France and the Association pour la Recherche sur le Cancer (VA and RAH)., Université Montpellier 1 ( UM1 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de Génétique Moléculaire de Montpellier ( IGMM ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Le Ster, Yves, and Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], MESH : Wound Healing, MESH : Promoter Regions, Genetic, MESH : RNA, Small Interfering, migration, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Mice, MESH : Phosphorylation, MESH : Cytoskeleton, 0302 clinical medicine, Desmosome organization, MESH: Cricetulus, MESH : CHO Cells, MESH: Animals, Cytoskeleton, Mitogen-Activated Protein Kinase 1, 0303 health sciences, Mitogen-Activated Protein Kinase 3, MESH : Gene Expression Regulation, MESH : Cricetinae, Keratinocyte activation, MESH: Transcription Factors, Cell biology, ErbB Receptors, 030220 oncology & carcinogenesis, MESH: Mitogen-Activated Protein Kinase 7, MESH: Mitogen-Activated Protein Kinase 3, MESH: Mitogen-Activated Protein Kinase 1, Slug, MESH : Cricetulus, MESH: Receptor, Epidermal Growth Factor, MESH: Cell Adhesion, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, MESH: CHO Cells, MESH: Promoter Regions, Genetic, Humans, Cell adhesion, Molecular Biology, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, EGF, MESH: Humans, Epidermal Growth Factor, MESH: Phosphorylation, [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology, HaCaT, MESH : Humans, MAPK, MESH : Epithelium, MESH: Wound Healing, MESH: Epithelium, Wound healing, [ SDV.MHEP.DERM ] Life Sciences [q-bio]/Human health and pathology/Dermatology, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, Transcription Factors, Keratinocytes, MESH: Epidermal Growth Factor, Cytoskeleton organization, MESH : Transcription Factors, MESH: Cricetinae, Epithelium, MESH : Receptor, Epidermal Growth Factor, Cricetinae, MESH: RNA, Small Interfering, Phosphorylation, RNA, Small Interfering, Keratinocyte migration, Promoter Regions, Genetic, MESH : Epidermal Growth Factor, MESH : Mitogen-Activated Protein Kinase 1, biology, MESH : Mitogen-Activated Protein Kinase 3, ERK1/2, MESH : Keratinocytes, [ SDV.MHEP.PHY ] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Articles, MESH: Gene Expression Regulation, MESH: Keratinocytes, MESH : Mitogen-Activated Protein Kinase 7, Motility, [SDV.CAN]Life Sciences [q-bio]/Cancer, CHO Cells, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Cricetulus, MESH : Mice, Cell Adhesion, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Cytoskeleton, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, MESH: Mice, Mitogen-Activated Protein Kinase 7, 030304 developmental biology, Wound Healing, Cell Biology, [SDV.MHEP.DERM] Life Sciences [q-bio]/Human health and pathology/Dermatology, biology.organism_classification, MESH : Cell Adhesion, Gene Expression Regulation, Cancer research, Snail Family Transcription Factors, MESH : Animals
Abstract: International audience; Reepithelialization during cutaneous wound healing involves numerous signals that result in basal keratinocyte activation, spreading, and migration, all linked to a loosening of cell-cell adhesion structures. The transcription factor Slug is required for this process, and EGF treatment of human keratinocytes induced activating phosphorylation of Erk5 that coincides with slug transcription. Accordingly, ectopic activation of Erk5 led to increased Slug mRNA levels and faster wound healing, whereas keratinocyte migration was totally blocked by Erk5 pathway inhibition. Expression of a shRNA specific for Erk5 strongly diminished Erk5 levels in keratinocytes and significantly decreased their motility response to EGF, along with induction of Slug expression. These Erk5-deprived keratinocytes showed an altered, more compact morphology, along with disruption of desmosome organization. Accordingly, they displayed an altered ability to form cell aggregates. These results implicate a novel EGFR/Erk5/Slug pathway in the control of cytoskeleton organization and cell motility in keratinocytes treated with EGF.
Published: 2008
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21. A novel dysfunctional LHX4 mutation with high phenotypical variability in patients with hypopituitarism

Author: Thierry Brue, Frédérique Albarel, Rachel Reynaud, Alexandru Saveanu, Raja Brauner, Marie-Helene Quentien, M. El Kholy, Alain Enjalbert, Anne-Marie Guedj, N. Kaffel, Anne Barlier, Frederic Castinetti, M. Amin, A. Buffin, Centre de recherche en neurobiologie - neurophysiologie de Marseille (CRN2M), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Interactions cellulaires neuroendocriniennes (ICN), Université de la Méditerranée - Aix-Marseille 2-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5), Aix Marseille Université (AMU) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), and Université de la Méditerranée - Aix-Marseille 2 - Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, MESH : Transcription Factors, MESH: Introns, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Electrophoretic Mobility Shift Assay, MESH : Genotype, Hypopituitarism, medicine.disease_cause, MESH: Hypopituitarism, Biochemistry, MESH: Genotype, 0302 clinical medicine, Endocrinology, MESH : Female, MESH : Homeodomain Proteins, Pituitary stalk, 0303 health sciences, Mutation, MESH: Middle Aged, MESH : Hypopituitarism, MESH: Transcription Factors, Middle Aged, MESH : Adult, Pedigree, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], 3. Good health, MESH : Phenotype, Phenotype, medicine.anatomical_structure, Sella turcica, MESH : Electrophoretic Mobility Shift Assay, Female, MESH : Mutation, Adult, medicine.medical_specialty, MESH: Mutation, Genotype, Somatotropic cell, MESH: Pedigree, MESH : Male, LIM-Homeodomain Proteins, 030209 endocrinology & metabolism, Context (language use), Biology, MESH: Phenotype, MESH : Introns, 03 medical and health sciences, [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Posterior pituitary, Internal medicine, MESH: Homeodomain Proteins, medicine, Humans, MESH : Middle Aged, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], 030304 developmental biology, Homeodomain Proteins, MESH: Humans, Biochemistry (medical), MESH : Humans, Heterozygote advantage, MESH: Adult, medicine.disease, Introns, MESH: Male, MESH : Pedigree, MESH: Electrophoretic Mobility Shift Assay, MESH: Female, Transcription Factors
Abstract: International audience; CONTEXT: LHX4 is a LIM homeodomain transcription factor involved in pituitary ontogenesis. Only a few heterozygous LHX4 mutations have been reported to be responsible for congenital pituitary hormone deficiency. SUBJECTS AND METHODS: A total of 136 patients with congenital hypopituitarism associated with malformations of brain structures, pituitary stalk, or posterior pituitary gland was screened for LHX4 mutations. RESULTS: Three novel allelic variants that cause predicted changes in the protein sequence of LHX4 (2.3%) were found (p.Thr99fs, p.Thr90Met, and p.Gly370Ser). On the basis of functional studies, p.Thr99fs mutation was responsible for the patients' phenotype, whereas p.Thr90Met and p.Gly370Ser were likely polymorphisms. Patients bearing the heterozygous p.Thr99fs mutation had variable phenotypes: two brothers presented somato-lactotroph and thyrotroph deficiencies, with pituitary hypoplasia and poorly developed sella turcica; the youngest brother (propositus) also had corpus callosum hypoplasia and ectopic neurohypophysis; their father only had somatotroph deficiency and delayed puberty with pituitary hyperplasia. Functional studies showed that the mutation induced a complete loss of transcriptional activity on POU1F1 promoter and a lack of DNA binding. Cotransfection of p.Thr99fs mutant and wild-type LHX4 failed to evidence any dominant negative effect, suggesting a mechanism of haploinsufficiency. We also identified prolactin and GH promoters as potential target genes of LHX4 and found that the p.Thr99fs mutant was also unable to transactivate these promoters. CONCLUSIONS: The present report describes three new exonic LHX4 allelic variants with at least one being responsible for congenital hypopituitarism. It also extends the phenotypical heterogeneity associated with LHX4 mutations, which includes variable anterior pituitary hormone deficits, as well as pituitary and extrapituitary abnormalities.
Published: 2008
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22. Two RNA polymerase I subunits control the binding and release of Rrn3 during transcription

Author: Beckouet, Frédéric, Labarre-Mariotte, Sylvie, Albert, Benjamin, Imazawa, Yukiko, Werner, Michel, Gadal, Olivier, Nogi, Yasuhisa, Kwapisz, Marta, BECKOUET, Frederic, Thuriaux, Pierre, Service de Biologie Intégrative et Génétique Moléculaire (SBIGeM), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Laboratoire de biologie moléculaire eucaryote (LBME), Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Service de Biologie Intégrative et Génétique Moléculaire ( SBIGeM ), Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de biologie moléculaire eucaryote du CNRS ( LBME ), Université Paul Sabatier - Toulouse 3 ( UPS ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), and Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Models, Molecular, MESH : Molecular Sequence Data, MESH : Transcription Factors, Transcription, Genetic, MESH: RNA Polymerase I, MESH: Sequence Homology, Amino Acid, [SDV]Life Sciences [q-bio], MESH : Protein Subunits, MESH : Saccharomyces cerevisiae, RNA polymerase II, MESH: Amino Acid Sequence, chemistry.chemical_compound, MESH : Mycophenolic Acid, 0302 clinical medicine, MESH: Saccharomyces cerevisiae Proteins, Sigma factor, RNA Polymerase I, RNA polymerase, Enzyme Inhibitors, ComputingMilieux_MISCELLANEOUS, Polymerase, MESH: Chromatin Immunoprecipitation, 0303 health sciences, biology, MESH : RNA Polymerase I, MESH : Amino Acid Sequence, MESH : Protein Binding, Articles, MESH: Transcription Factors, MESH : Schizosaccharomyces pombe Proteins, MESH: Protein Subunits, MESH: Saccharomyces cerevisiae, MESH : Sequence Homology, Amino Acid, MESH: Schizosaccharomyces, MESH : Dimerization, MESH: Enzyme Inhibitors, Transcription factor II D, MESH : Mutation, Dimerization, Pol1 Transcription Initiation Complex Proteins, MESH: Models, Molecular, Plasmids, Protein Binding, MESH : Pol1 Transcription Initiation Complex Proteins, Chromatin Immunoprecipitation, Saccharomyces cerevisiae Proteins, MESH: Mutation, MESH : Models, Molecular, Termination factor, Molecular Sequence Data, RNA-dependent RNA polymerase, Saccharomyces cerevisiae, MESH: Two-Hybrid System Techniques, MESH : Saccharomyces cerevisiae Proteins, 03 medical and health sciences, MESH : Chromatin Immunoprecipitation, MESH: Plasmids, Two-Hybrid System Techniques, Schizosaccharomyces, RNA polymerase I, MESH: Protein Binding, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Amino Acid Sequence, MESH: Pol1 Transcription Initiation Complex Proteins, Molecular Biology, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, MESH: Mycophenolic Acid, MESH : Enzyme Inhibitors, MESH: Molecular Sequence Data, Sequence Homology, Amino Acid, MESH: Transcription, Genetic, MESH : Transcription, Genetic, MESH: Schizosaccharomyces pombe Proteins, Cell Biology, Mycophenolic Acid, Molecular biology, Protein Subunits, chemistry, MESH : Schizosaccharomyces, MESH : Two-Hybrid System Techniques, MESH: Dimerization, MESH : Plasmids, Mutation, biology.protein, Schizosaccharomyces pombe Proteins, 030217 neurology & neurosurgery, Transcription Factors
Abstract: International audience; Rpa34 and Rpa49 are nonessential subunits of RNA polymerase I, conserved in species from Saccharomyces cerevisiae and Schizosaccharomyces pombe to humans. Rpa34 bound an N-terminal region of Rpa49 in a two-hybrid assay and was lost from RNA polymerase in an rpa49 mutant lacking this Rpa34-binding domain, whereas rpa34Delta weakened the binding of Rpa49 to RNA polymerase. rpa34Delta mutants were caffeine sensitive, and the rpa34Delta mutation was lethal in a top1Delta mutant and in rpa14Delta, rpa135(L656P), and rpa135(D395N) RNA polymerase mutants. These defects were shared by rpa49Delta mutants, were suppressed by the overexpression of Rpa49, and thus, were presumably mediated by Rpa49 itself. rpa49 mutants lacking the Rpa34-binding domain behaved essentially like rpa34Delta mutants, but strains carrying rpa49Delta and rpa49-338::HIS3 (encoding a form of Rpa49 lacking the conserved C terminus) had reduced polymerase occupancy at 30 degrees C, failed to grow at 25 degrees C, and were sensitive to 6-azauracil and mycophenolate. Mycophenolate almost fully dissociated the mutant polymerase from its ribosomal DNA (rDNA) template. The rpa49Delta and rpa49-338::HIS3 mutations had a dual effect on the transcription initiation factor Rrn3 (TIF-IA). They partially impaired its recruitment to the rDNA promoter, an effect that was bypassed by an N-terminal deletion of the Rpa43 subunit encoded by rpa43-35,326, and they strongly reduced the release of the Rrn3 initiation factor during elongation. These data suggest a dual role of the Rpa49-Rpa34 dimer during the recruitment of Rrn3 and its subsequent dissociation from the elongating polymerase.
Published: 2008
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23. PAI-1 and functional blockade of SNAI1 in breast cancer cell migration

Author: José Palacios, Amparo Cano, Amandine Cartier-Michaud, Gema Moreno-Bueno, Elizabeth Fabre-Guillevin, Benoît Vallée, Michel Malo, Georgia Barlovatz-Meimon, Daniel A. Lawrence, Héctor Peinado, Cécile Charrière-Bertrand, Hôpital Européen Georges Pompidou [APHP] (HEGP), DYNAMIC, Informatique, Biologie Intégrative et Systèmes Complexes (IBISC), Université d'Évry-Val-d'Essonne (UEVE) - Centre National de la Recherche Scientifique (CNRS) - Université d'Évry-Val-d'Essonne (UEVE) - Centre National de la Recherche Scientifique (CNRS), Centre National d'Investigations Oncologiques (CNIO), CNIO, Laboratoire de recherche sur la croissance cellulaire, la réparation et la régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12) - Centre National de la Recherche Scientifique (CNRS), Servicio de Anatomia Patologica, Hospital Virgen del Rocío, Université d'Évry-Val-d'Essonne (UEVE) - Centre National de la Recherche Scientifique (CNRS) - Université d'Évry-Val-d'Essonne (UEVE) - Centre National de la Recherche Scientifique (CNRS) - Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Spanish National Cancer Research Center (CNIO), Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Hospital Universitario Virgen del Rocío [Sevilla], and Centre National de la Recherche Scientifique (CNRS)-Université d'Évry-Val-d'Essonne (UEVE)
Subjects: MESH : RNA, Messenger, MESH : Transcription Factors, MESH : Wound Healing, Fluorescent Antibody Technique, Snail, MESH : Breast Neoplasms, MESH: Cadherins, MESH: Plasminogen Activator Inhibitor 1, Metastasis, Immunoenzyme Techniques, chemistry.chemical_compound, 0302 clinical medicine, MESH : Tumor Cells, Cultured, Cell Movement, MESH: Reverse Transcriptase Polymerase Chain Reaction, Tumor Cells, Cultured, MESH : Cell Movement, MESH : Female, Pseudopodia, Receptor, MESH: Cell Movement, MESH: Fluorescent Antibody Technique, Genes, Dominant, Oligonucleotide Array Sequence Analysis, Medicine(all), 0303 health sciences, Reverse Transcriptase Polymerase Chain Reaction, MESH : Reverse Transcriptase Polymerase Chain Reaction, Cell migration, MESH : Urokinase-Type Plasminogen Activator, MESH: Transcription Factors, MESH : Genes, Dominant, Cadherins, 3. Good health, MESH : Oligonucleotide Array Sequence Analysis, 030220 oncology & carcinogenesis, Plasminogen activator inhibitor-1, Female, MESH : Cadherins, Research Article, MESH : Plasminogen Activator Inhibitor 1, Breast Neoplasms, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, MESH: Urokinase-Type Plasminogen Activator, MESH: Gene Expression Profiling, 03 medical and health sciences, MESH : Immunoenzyme Techniques, biology.animal, Plasminogen Activator Inhibitor 1, medicine, Humans, RNA, Messenger, MESH: Tumor Cells, Cultured, MESH: Immunoenzyme Techniques, Cell adhesion, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, MESH: RNA, Messenger, 030304 developmental biology, Wound Healing, MESH: Humans, Gene Expression Profiling, MESH : Gene Expression Profiling, MESH : Humans, Cancer, medicine.disease, Urokinase-Type Plasminogen Activator, Molecular biology, MESH: Wound Healing, MESH : Fluorescent Antibody Technique, chemistry, MESH: Pseudopodia, MESH: Oligonucleotide Array Sequence Analysis, SNAI1, MESH : Pseudopodia, Cancer research, Snail Family Transcription Factors, MESH: Genes, Dominant, MESH: Female, MESH: Breast Neoplasms, Transcription Factors
Abstract: International audience; INTRODUCTION: Snail, a family of transcriptional repressors implicated in cell movement, has been correlated with tumour invasion. The Plasminogen Activation (PA) system, including urokinase plasminogen activator (uPA), its receptor and its inhibitor, plasminogen activator inhibitor type 1(PAI-1), also plays a key role in cancer invasion and metastasis, either through proteolytic degradation or by non-proteolytic modulation of cell adhesion and migration. Thus, Snail and the PA system are both over-expressed in cancer and influence this process. In this study we aimed to determine if the activity of SNAI1 (a member of the Snail family) is correlated with expression of the PA system components and how this correlation can influence tumoural cell migration. METHODS: We compared the invasive breast cancer cell-line MDA-MB-231 expressing SNAI1 (MDA-mock) with its derived clone expressing a dominant-negative form of SNAI1 (SNAI1-DN). Expression of PA system mRNAs was analysed by cDNA microarrays and real-time quantitative RT-PCR. Wound healing assays were used to determine cell migration. PAI-1 distribution was assessed by immunostaining. RESULTS: We demonstrated by both cDNA microarrays and real-time quantitative RT-PCR that the functional blockade of SNAI1 induces a significant decrease of PAI-1 and uPA transcripts. After performing an in vitro wound-healing assay, we observed that SNAI1-DN cells migrate more slowly than MDA-mock cells and in a more collective manner. The blockade of SNAI1 activity resulted in the redistribution of PAI-1 in SNAI1-DN cells decorating large lamellipodia, which are commonly found structures in these cells. CONCLUSIONS: In the absence of functional SNAI1, the expression of PAI-1 transcripts is decreased, although the protein is redistributed at the leading edge of migrating cells in a manner comparable with that seen in normal epithelial cells.
Published: 2008
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24. Loss of Trim24 (Tif1alpha) gene function confers oncogenic activity to retinoic acid receptor alpha

Author: Johan Tisserand, Daniel Metzger, Pierre Chambon, Benjamin Herquel, Florence Cammas, Marius Teletin, Mihaela Ignat, Christelle Thibault, Konstantin Khetchoumian, Thierry Lerouge, Manuel Mark, Jessica Zucman-Rossi, Régine Losson, Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Louis Pasteur - Strasbourg I, Labex Immuno-oncology, Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-PRES Sorbonne Paris Cité-Faculté de Médecine, Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Institut de génétique et biologie moléculaire et cellulaire ( IGBMC ), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de Recherche des Cordeliers ( CRC ), Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -PRES Sorbonne Paris Cité-Faculté de Médecine, and Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-PRES Sorbonne Paris Cité-Faculté de Médecine
Subjects: MESH : Liver Neoplasms, MESH : Transcription Factors, Receptors, Retinoic Acid, Retinoic acid, Retinoic acid receptor beta, MESH : Hepatocytes, MESH: Hepatocytes, Mice, chemistry.chemical_compound, 0302 clinical medicine, MESH: Liver Neoplasms, MESH : Cell Proliferation, Genes, Tumor Suppressor, MESH: Animals, MESH: Carcinoma, Hepatocellular, 0303 health sciences, Retinoic Acid Receptor alpha, Liver Neoplasms, Nuclear Proteins, MESH: Transcription Factors, MESH : Receptors, Retinoic Acid, 030220 oncology & carcinogenesis, MESH : Carcinoma, Hepatocellular, Carcinoma, Hepatocellular, MESH : Genes, Tumor Suppressor, [ SDV.BBM.BM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Biology, Retinoic acid-inducible orphan G protein-coupled receptor, 03 medical and health sciences, MESH: Cell Proliferation, MESH : Mice, Genetics, Animals, MESH: Mice, Cell Proliferation, 030304 developmental biology, MESH: Receptors, Retinoic Acid, Retinoid X receptor alpha, MESH : Nuclear Proteins, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Retinoic acid receptor gamma, MESH: Genes, Tumor Suppressor, Retinoid X receptor gamma, Retinoic acid receptor, chemistry, Retinoic acid receptor alpha, Hepatocytes, Cancer research, MESH : Animals, MESH: Nuclear Proteins, Transcription Factors
Abstract: Hepatocellular carcinoma (HCC) is a major cause of death worldwide. Here, we provide evidence that the ligand-dependent nuclear receptor co-regulator Trim24 (also known as Tif1alpha) functions in mice as a liver-specific tumor suppressor. In Trim24-null mice, hepatocytes fail to execute proper cell cycle withdrawal during the neonatal-to-adult transition and continue to cycle in adult livers, becoming prone to a continuum of cellular alterations that progress toward metastatic HCC. Using pharmacological approaches, we show that inhibition of retinoic acid signaling markedly reduces hepatocyte proliferation in Trim24-/- mice. We further show that deletion of a single retinoic acid receptor alpha (Rara) allele in a Trim24-null background suppresses HCC development and restores wild-type expression of retinoic acid-responsive genes in the liver, thus demonstrating that in this genetic background Rara expresses an oncogenic activity correlating with a dysregulation of the retinoic acid signaling pathway. Our results not only provide genetic evidence that Trim24 and Rara co-regulate hepatocarcinogenesis in an antagonistic manner but also suggest that aberrant activation of Rara is deleterious to liver homeostasis.
Published: 2007
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25. HNF1alpha inactivation promotes lipogenesis in human hepatocellular adenoma independently of SREBP-1 and carbohydrate-response element-binding protein (ChREBP) activation

Author: Sandrine Imbeaud, Justine Bertrand-Michel, Sandra Rebouissou, Charles Auffray, Charles Balabaud, François Tercé, Paulette Bioulac-Sage, Virginie Boulanger, Jessica Zucman-Rossi, Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Labex Immuno-oncology, Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-PRES Sorbonne Paris Cité-Faculté de Médecine, Génétique moléculaire de la neurotransmission et des processus neurodégénératifs (LGMNPN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Fibrose hépatique et cancer du foie, Université Bordeaux Segalen - Bordeaux 2-IFR66-Institut National de la Santé et de la Recherche Médicale (INSERM), Plateau MetaToul-LIPIDOMIQUE = MetaToul-Lipidomics, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, This work was supported by the Inserm (Réseau de Recherche clinique et en santé des populations), ARC n°5188, SNFGE and the Fondation de France. SR is supported by a Ligue Nationale Contre le Cancer doctoral fellowship., Zucman-Rossi, Jessica, Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-PRES Sorbonne Paris Cité-Faculté de Médecine, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-MetaboHUB-MetaToul, Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), MetaToul Lipidomics, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-MetaboHUB-MetaToul, MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Genomique Fonctionnelle des Tumeurs Solides, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ) -IFR105-Université Paris Diderot - Paris 7 ( UPD7 ), Centre de Recherche des Cordeliers ( CRC ), Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -PRES Sorbonne Paris Cité-Faculté de Médecine, Génétique moléculaire de la neurotransmission et des processus neurodégénératifs ( LGMNPN ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ), Université Bordeaux Segalen - Bordeaux 2-IFR66-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Plateau de lipidomique, Hôpital Purpan [Toulouse], and CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Claude de Preval
Subjects: Male, Biochemistry, 0302 clinical medicine, MESH: Liver Neoplasms, Glycolysis, MESH : Glycolysis, Oligonucleotide Array Sequence Analysis, chemistry.chemical_classification, 0303 health sciences, MESH: Middle Aged, Fatty Acids, Liver Neoplasms, MESH: SREBP-1, MESH: Transcription Factors, Gene Expression Regulation, Neoplastic, MESH : Oligonucleotide Array Sequence Analysis, MESH: Promoter Regions (Genetics), 030220 oncology & carcinogenesis, MESH : Hepatocyte Nuclear Factor 1-alpha, [ SDV.MHEP.HEG ] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Sterol Regulatory Element Binding Protein 1, MESH: Citric Acid, MESH : Gene Expression Regulation, Neoplastic, Adenoma, Liver Cell, 03 medical and health sciences, MESH: Gene Expression Profiling, MESH: Sterol Regulatory Element Binding Protein 1, MESH : steatosis, MESH : Adenoma, Liver Cell, MESH : Sterol Regulatory Element Binding Protein 1, MESH : Adolescent, Humans, MESH : Middle Aged, MESH: Hepatocyte Nuclear Factor 1-alpha, Molecular Biology, Fatty acid synthesis, MESH: Lipogenesis, MESH: Adolescent, MESH: Humans, MESH : Gene Expression Profiling, MESH : Humans, Fatty acid, MESH : HNF1α, MESH: Adult, medicine.disease, MESH : Promoter Regions (Genetics), Sterol regulatory element-binding protein, chemistry, MESH: Tumor Markers, Biological, MESH : Response Elements, MESH: Female, Transcription Factors, MESH: Liver, MESH: Signal Transduction, MESH : Liver Neoplasms, MESH : Fatty Liver, MESH : Transcription Factors, chemistry.chemical_compound, MESH: Adenoma, Liver Cell, MESH : Tumor Markers, Biological, MESH : Female, Hepatocyte Nuclear Factor 1-alpha, Promoter Regions, Genetic, MESH : Fatty Acids, MESH: Fatty Liver, MESH: Gluconeogenesis, MESH: Gene Expression Regulation, Neoplastic, Middle Aged, MESH : Adult, MESH: Fatty Acids, Liver, Lipogenesis, MESH: Glycolysis, Female, MESH: Response Elements, MESH : SREBP-1, Signal Transduction, Adult, Adolescent, MESH : Male, MESH : Gluconeogenesis, MESH : Citric Acid, Biology, Response Elements, Citric Acid, MESH: steatosis, Biomarkers, Tumor, medicine, MESH : hepatocellular adenoma, Carbohydrate-responsive element-binding protein, Transcription factor, 030304 developmental biology, MESH : Signal Transduction, Gene Expression Profiling, MESH: hepatocellular adenoma, Gluconeogenesis, MESH : Liver, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Cell Biology, MESH: HNF1α, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, MESH: Male, MESH : Lipogenesis, Fatty Liver, MESH: Oligonucleotide Array Sequence Analysis, Steatosis
Abstract: International audience; Biallelic inactivating mutations of the transcription factor 1 gene (TCF1), encoding hepatocyte nuclear factor 1alpha (HNF1alpha) were identified in 50% of hepatocellular adenomas (HCA) phenotypically characterized by a striking steatosis. To understand the molecular basis of this aberrant lipid storage, we performed a microarray transcriptome analysis validated by quantitative reverse transcription-PCR, Western blotting, and lipid profiling. In mutated HCA, we showed a repression of gluconeogenesis coordinated with an activation of glycolysis, citrate shuttle, and fatty acid synthesis predicting elevated rates of lipogenesis. Moreover, the strong down-regulation of liver fatty acid-binding protein suggests that impaired fatty acid trafficking may also contribute to the fatty phenotype. In addition, transcriptional profile analysis of the observed deregulated genes in non-HNF1alpha-mutated HCA as well as in non-tumor livers allowed us to define a specific signature of the HNF1alpha-mutated HCA. In these tumors, lipid composition was dramatically modified according to the transcriptional deregulations identified in the fatty acid synthetic pathway. Surprisingly, lipogenesis activation did not operate through sterol regulatory element-binding protein-1 (SREBP-1) and carbohydrate-response element-binding protein (ChREBP) that were repressed. We conclude that steatosis in HNF1alpha-mutated HCA results mainly from an aberrant promotion of lipogenesis that is linked to HNF1alpha inactivation and that is independent of both SREBP-1 and ChREBP activation. Finally, our findings have potential clinical implications since lipogenesis can be efficiently inhibited by targeted therapies.
Published: 2007
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26. Analysis of the fiber architecture of the heart by quantitative polarized light microscopy. Accuracy, limitations and contribution to the study of the fiber architecture of the ventricles during fetal and neonatal life

Author: Ayman Mourad, Gabrielle Michalowicz, Pierre-Simon Jouk, Annie Raoult, Yves Usson, Denis Caillerie, Vuk Milisic, RFMQ, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Equations aux Dérivées Partielles (EDP), Laboratoire Jean Kuntzmann (LJK), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS), Mathématiques Appliquées Paris 5 (MAP5 - UMR 8145), Université Paris Descartes - Paris 5 (UPD5)-Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS), Laboratoire sols, solides, structures - risques [Grenoble] (3SR), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications [Grenoble] ( TIMC-IMAG ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -IMAG-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -IMAG-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Equations aux Dérivées Partielles ( EDP ), Laboratoire Jean Kuntzmann ( LJK ), Université Pierre Mendès France - Grenoble 2 ( UPMF ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Université Pierre Mendès France - Grenoble 2 ( UPMF ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Mathématiques Appliquées à Paris 5 ( MAP5 - UMR 8145 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National des Sciences Mathématiques et de leurs Interactions-Centre National de la Recherche Scientifique ( CNRS ), Laboratoire sols, solides, structures - risques [Grenoble] ( 3S-R ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut National Polytechnique de Grenoble ( INPG ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), and Centre National de la Recherche Scientifique (CNRS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Université Joseph Fourier - Grenoble 1 (UJF)-Université Pierre Mendès France - Grenoble 2 (UPMF)-Centre National de la Recherche Scientifique (CNRS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Université Joseph Fourier - Grenoble 1 (UJF)-Université Pierre Mendès France - Grenoble 2 (UPMF)
Subjects: MESH: Neoplasm Proteins, MESH : Transcription Factors, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, MESH : DNA, Muscle Fibers, Skeletal, MESH : Models, Biological, 030204 cardiovascular system & hematology, Tracking (particle physics), 030218 nuclear medicine & medical imaging, Section (fiber bundle), MESH : Muscle Fibers, 0302 clinical medicine, Orientation (geometry), MESH : Myocardium, Medicine, MESH : G2 Phase, Fiber, MESH : Adaptation, Physiological, [ SDV.IB.IMA ] Life Sciences [q-bio]/Bioengineering/Imaging, Polarized light microscopy, MESH : Tumor Suppressor Proteins, MESH: Infant, Newborn, MESH: Muscle Fibers, MESH: DNA, MESH : Protein Binding, General Medicine, MESH: Transcription Factors, Adaptation, Physiological, Azimuth, MESH: Reproducibility of Results, MESH: Heterochromatin, MESH: Microscopy, Polarization, Microscopy, Polarization, Cardiology and Cardiovascular Medicine, MESH : Chromosomal Proteins, Non-Histone, Pulmonary and Respiratory Medicine, MESH: Cell Line, Tumor, MESH: Myocardium, Heart Ventricles, MESH : Infant, Newborn, Models, Biological, 03 medical and health sciences, Optics, Fetal Heart, MESH : Neoplasm Proteins, MESH: Chromosomal Proteins, Non-Histone, Humans, MESH: Protein Binding, MESH: Tumor Suppressor Proteins, MESH : Microscopy, Polarization, MESH: Humans, Pixel, Plane (geometry), business.industry, MESH : Cell Line, Tumor, MESH : Heterochromatin, Myocardium, MESH : Reproducibility of Results, MESH : Humans, Infant, Newborn, MESH: Models, Biological, Reproducibility of Results, MESH : Nuclear Proteins, MESH : Fetal Heart, MESH: Adaptation, Physiological, MESH: G2 Phase, MESH: Fetal Heart, MESH : Heart Ventricles, Surgery, MESH: Heart Ventricles, business, MESH: Nuclear Proteins
Abstract: International audience; OBJECTIVE: To address the advantages and drawbacks of quantitative polarized light microscopy for the study of myocardial cell orientation and to identify its contribution in the field. METHODS: Quantitative polarized light microscopy allows to measure the orientation of myocardial fibers into the ventricular mass. For each pixel of a horizontal section, this orientation is the mean value of the directions of all myosin filaments contained in the thickness of the section for each pixel of the section and is accounted for by two angles, the azimuth angle, which is the angle of the fiber in the plane of the section, and the elevation angle, which measures the way the fiber escapes from the section. The azimuth is accurately measured, and its range of definition is complete from 0 degrees to 180 degrees . The elevation angle can be defined only in the range 0 degrees to 90 degrees . It is accurately measured between 20 degrees and 70 degrees . From 0 degrees to 20 degrees , there is a systematic bias raising the measured values, and from 70 degrees to 90 degrees , the angle is not accurately measured. RESULTS: With this method, we validated Streeter's conjecture concerning the architecture of the left ventricle. We formulated a pretzel conjecture about the fiber architecture of the whole ventricular mass during fetal period. In our model, elaborated by visual analysis of registered maps of orientation, the fibers run like geodesics on a nested set of 'pretzels'. Next, the validity of the helical ventricular myocardial band model of Torrent-Guasp has been examined. It appears that the band model does not account for the patterns observed in our data during the fetal period. However, after the major events of postnatal cardiovascular adaptation, our data can neither discard nor confirm Torrent-Guasp's model. CONCLUSIONS: Present limitations of quantitative polarized light analysis can neither confirm nor discard the existing models of fiber orientation in the whole ventricular mass after the neonatal period. However, the problems of mathematical and experimental validation of these two models have been posed in a rigorous manner. Non-ambiguous fiber tracking and demonstration of these models will require significant improvement of the definition range of the elevation angle that should be extended to 180 degrees .
Published: 2007
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27. HDAC6 controls major cell response pathways to cytotoxic accumulation of protein aggregates

Author: Cyril Boyault, Benoit Gilquin, Yu Zhang, Carmen Garrido, Cécile Caron, Patrick Matthias, Saadi Khochbin, So Hee Kwon, Claire Vourc'h, Sabrina Fritah, Tso-Pang Yao, Souchier, Catherine, Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Friedrich Miescher Institute for Biomedical Research (FMI), Novartis Research Foundation, Mort cellulaire et cancer, Université de Bourgogne (UB)-IFR100 - Structure fédérative de recherche Santé-STIC-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Pharmacology and Cancer Biology, Duke University [Durham], INSERM U823, équipe 10 (Stress et Dynamique de l'Organisation du Génome), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), INSERM U823, équipe 6 (Epigénétique et Signalisation Cellulaire), Institut d'oncologie/développement Albert Bonniot de Grenoble ( INSERM U823 ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Friedrich Miescher Institute for Biomedical Research ( FMI ), Université de Bourgogne ( UB ) -IFR100 - Structure fédérative de recherche Santé-STIC-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Duke university [Durham], and Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale ( INSERM )
Subjects: Protein Folding, MESH : Transcription Factors, MESH: 3T3 Cells, Leupeptins, Cell Cycle Proteins, MESH: Tubulin, Protein aggregation, Histone Deacetylase 6, Mice, MESH : Cell Cycle Proteins, 0302 clinical medicine, Heat Shock Transcription Factors, MESH : Leupeptins, Tubulin, Valosin Containing Protein, MESH: Animals, Nuclear protein, HSF1, MESH: HSP70 Heat-Shock Proteins, MESH : Ubiquitin, Adenosine Triphosphatases, 0303 health sciences, MESH : Histone Deacetylases, Nuclear Proteins, MESH : Protein Binding, Acetylation, 3T3 Cells, MESH: Transcription Factors, MESH : Tubulin, MESH : HSP90 Heat-Shock Proteins, MESH : Heat-Shock Response, Hsp90, Cell biology, DNA-Binding Proteins, Aggresome, 030220 oncology & carcinogenesis, MESH : DNA-Binding Proteins, MESH: Molecular Chaperones, MESH: Acetylation, MESH : Protein Folding, MESH : 3T3 Cells, Protein Binding, Research Paper, MESH: Ubiquitin, MESH: Protein Folding, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, MESH : Acetylation, Histone Deacetylases, 03 medical and health sciences, MESH: Cell Cycle Proteins, MESH : Mice, Genetics, MESH: Adenosine Triphosphatases, MESH: HSP90 Heat-Shock Proteins, Animals, MESH: Protein Binding, HSP70 Heat-Shock Proteins, HSP90 Heat-Shock Proteins, Cell Cycle Protein, Transcription factor, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, MESH: Mice, 030304 developmental biology, MESH : Adenosine Triphosphatases, [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology, Ubiquitin, MESH : Molecular Chaperones, MESH : Nuclear Proteins, MESH : HSP70 Heat-Shock Proteins, MESH: Leupeptins, HDAC6, MESH: Histone Deacetylases, MESH: Heat-Shock Response, biology.protein, MESH : Animals, MESH: Nuclear Proteins, Heat-Shock Response, MESH: DNA-Binding Proteins, Molecular Chaperones, Transcription Factors, Developmental Biology
Abstract: International audience; A cellular defense mechanism counteracts the deleterious effects of misfolded protein accumulation by eliciting a stress response. The cytoplasmic deacetylase HDAC6 (histone deacetylase 6) was previously shown to be a key element in this response by coordinating the clearance of protein aggregates through aggresome formation and their autophagic degradation. Here, for the first time, we demonstrate that HDAC6 is involved in another crucial cell response to the accumulation of ubiquitinated protein aggregates, and unravel its molecular basis. Indeed, our data show that HDAC6 senses ubiquitinated cellular aggregates and consequently induces the expression of major cellular chaperones by triggering the dissociation of a repressive HDAC6/HSF1 (heat-shock factor 1)/HSP90 (heat-shock protein 90) complex and a subsequent HSF1 activation. HDAC6 therefore appears as a master regulator of the cell protective response to cytotoxic protein aggregate formation.
Published: 2007
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28. The Genome of the Sea Urchin Strongylocentrotus purpuratus

Author: Amro Hamdoun, Virginia Brockton, Huyen Dinh, Qiang Tu, Richard O. Hynes, Maria Ina Arnone, Wratko Hlavina, L. Courtney Smith, Mariano A. Loza, David R. Burgess, Matthew P. Hoffman, Florian Raible, Qiu Autumn Yuan, Geoffrey Okwuonu, Mark Y. Tong, Jennifer Hume, Donna Maglott, Manisha Goel, Olivier Fedrigo, Manuel L. Gonzalez-Garay, Celina E. Juliano, Judith Hernandez, Gary M. Wessel, William F. Marzluff, Audrey J. Majeske, Christian Gache, Louise Duloquin, Xingzhi Song, François Lapraz, Fowler J, Alexandre Souvorov, Jared V. Goldstone, Georgia Panopoulou, Sandra Hines, Kyle M. Judkins, Clay Davis, Christine G. Elsik, Paul Kitts, Mariano Loza-Coll, Greg Wray, Taku Hibino, Eric Röttinger, Allison M. Churcher, Annamaria Locascio, Arcady Mushegian, Masashi Kinukawa, Anna Reade, Katherine M. Buckley, I. R. Gibbons, Bert Gold, Aleksandar Milosavljevic, David Epel, Victor D. Vacquier, Ling Ling Pu, Vincenzo Cavalieri, Erin L. Allgood, Lan Zhang, Lynne V. Nazareth, Constantin N. Flytzanis, Ian Bosdet, Yi-Hsien Su, Zeev Pancer, Matthew L. Rowe, Robert C. Angerer, David R. McClay, William H. Klein, Rachel F. Gray, Julian L. Wong, Shunsuke Yaguchi, Robert Bellé, Aaron J. Mackey, Herath Jayantha Gunaratne, Karl Frederik Bergeron, Bruce P. Brandhorst, Greg Murray, Avis H. Cohen, Stephanie Bell, Kristin Tessmar-Raible, Ian K. Townley, Bertrand Cosson, Thomas D. Glenn, Jongmin Nam, Cynthia A. Bradham, Michael Dean, Joseph Chacko, Anthony J. Robertson, Margherita Branno, Valeria Matranga, K. James Durbin, Esther Miranda, Lili Chen, Eran Elhaik, Robert D. Burke, Rita A. Wright, Paola Oliveri, Sandra L. Lee, Gary W. Moy, Alexander E Primus, Shawn S. McCafferty, Cristina Calestani, David A. Garfield, Erica Sodergren, Karen Wilson, Joel Smith, Marco A. Marra, Cynthia Messier, Julia Morales, Kim D. Pruitt, Rachel Thorn, Rachel Gill, John S. Taylor, Mark E. Hahn, Victor Sapojnikov, Meredith Howard-Ashby, Lynne M. Angerer, Maurice R. Elphick, Kathy R. Foltz, Anne Marie Genevière, Justin T. Reese, Blanca E. Galindo, Kim C. Worley, Andrew Leone, Glen Humphrey, Kevin Berney, Olga Ermolaeva, George Miner, David P. Terwilliger, Elly Suk Hen Chow, Lora Lewis, Dan Graur, C. Titus Brown, Gerard Manning, Kevin J. Peterson, Angela Jolivet, Michele K. Anderson, Francesca Rizzo, Ekaterina Voronina, Thierry Lepage, Giorgio Matassi, Antonio Fernandez-Guerra, Mamoru Nomura, Charles A. Whittaker, James R.R. Whittle, James A. Coffman, George M. Weinstock, Mohammed M. Idris, Ashlan M. Musante, Sebastian D. Fugmann, Katherine D. Walton, Sorin Istrail, Shu-Yu Wu, Cerrissa Hamilton, Jonah Cool, Jacqueline E. Schein, Stacey M. Curry, Athula Wikramanayke, Seth Carbonneau, Blair J. Rossetti, Christopher E. Killian, Melissa J. Landrum, Amanda P. Rawson, Jenifer C. Croce, Ryan C. Range, Rahul Satija, John J. Stegeman, Yufeng Shen, Cavit Agca, Terry Gaasterland, Rocky Cheung, Takae Kiyama, Nikki Adams, Jonathan P. Rast, Robert Piotr Olinski, Andrew Cree, Mark Scally, Shuguang Liang, David A. Parker, Rebecca Thomason, Gretchen E. Hofmann, Michelle M. Roux, Ronghui Xu, Robert A. Obar, Enrique Arboleda, Odile Mulner-Lorillon, Shannon Dugan-Rocha, David J. Bottjer, Gabriele Amore, Manoj P. Samanta, Waraporn Tongprasit, Véronique Duboc, La Ronda Jackson, Fred H. Wilt, Viktor Stolc, Anna T. Neill, Michael Raisch, Pei Yun Lee, Jia L. Song, Margaret Morgan, Brian T. Livingston, Sofia Hussain, Zheng Wei, Bryan J. Cole, Tonya F. Severson, Victor V. Solovyev, Finn Hallböök, Donna M. Muzny, Christine A. Byrum, Albert J. Poustka, Xiuqian Mu, Andrew R. Jackson, Shin Heesun, Euan R. Brown, Nansheng Chen, Patrick Cormier, Ralph Haygood, Pedro Martinez, R. Andrew Cameron, D. Wang, Wendy S. Beane, Eric H. Davidson, Christie Kovar, Hemant Kelkar, Charles A. Ettensohn, Sham V. Nair, Robert L. Morris, Stefan C. Materna, Michael C. Thorndyke, Richard A. Gibbs, Dan O Mellott, Department of Physiology and Biophysics, Stony Brook University [The State University of New York] ( SBU ), Astronomy Unit ( AU ), Queen Mary University of London ( QMUL ), Urban and Industrial Air Quality Group, CSIRO Energy Technology, Commonwealth Scientific and Industrial Research Organisation Energy Technology ( CSIRO Energy Technology ), Commonwealth Scientific and Industrial Research Organisation, Center for Polymer Studies ( CPS ), Boston University [Boston] ( BU ), Physics Department [Boston] ( BU-Physics ), Max Planck Institute for Psycholinguistics, Max-Planck-Institut, Department of Biology [Norton], Wheaton College [Norton], Mathematical Institute [Oxford] ( MI ), University of Oxford [Oxford], Centre for the Analysis of Time Series ( CATS ), London School of Economics and Political Science ( LSE ), Thomas Jefferson National Accelerator Facility ( Jefferson Lab ), Thomas Jefferson National Accelerator Facility, Laboratoire d'Energétique et de Mécanique Théorique Appliquée ( LEMTA ), Université de Lorraine ( UL ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire Evolution, Génomes et Spéciation ( LEGS ), Centre National de la Recherche Scientifique ( CNRS ), Department of Geology, University of Illinois at Urbana-Champaign [Urbana], Department of Electrical and Computer Engineering [Portland] ( ECE ), Portland State University [Portland] ( PSU ), Saint-Gobain Crystals [USA], SAINT-GOBAIN, Institute for Animal Health ( IAH ), Biotechnology and Biological Sciences Research Council, Center for Agricultural Resources Research, Chinese Academy of Sciences [Changchun Branch] ( CAS ), Ipsen Inc. [Milford] ( Ipsen ), IPSEN, Department of Physics [Berkeley], University of California [Berkeley], Institute for Climate and Atmospheric Science [Leeds] ( ICAS ), University of Leeds, Chung-Ang University ( CAU ), Chung-Ang University [Seoul], Antarctic Climate and Ecosystems Cooperative Research Center ( ACE-CRC ), Institute of Aerodynamics and Fluid Mechanics ( AER ), Technische Universität München [München] ( TUM ), Mer et santé ( MS ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ), Imperial College London, Radio and Atmospheric Sciences Division, National Physical Laboratory [Teddington] ( NPL ), International Research Institute for Climate and Society ( IRI ), Earth Institute at Columbia University, Columbia University [New York]-Columbia University [New York], Soils Group, The Macaulay Institute, Department of Haematology, University of Cambridge [UK] ( CAM ), School of Biology and Biochemistry, Queen's University, Leslie Hill Institute for Plant Conservation ( PCU ), University of Cape Town, Institute for Microelectronics and Microsystems/ Istituto per la Microelettronica e Microsistemi ( IMM ), Consiglio Nazionale delle Ricerche ( CNR ), Laboratoire d'acoustique de l'université du Mans ( LAUM ), Le Mans Université ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Interactive Systems Labs ( ISL ), Carnegie Mellon University [Pittsburgh] ( CMU ), Dalian Institute of Chemical Physics ( DICP ), Architectures, Languages and Compilers to Harness the End of Moore Years ( ALCHEMY ), Laboratoire de Recherche en Informatique ( LRI ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ) -Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ) -Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique ( Inria ), Clean Air Task Force ( CATF ), Clean Air Task Force, Space Physics Laboratory, Indian Space Research Organisation ( ISRO ), Centre d'études et de recherches appliquées à la gestion ( CERAG ), Université Pierre Mendès France - Grenoble 2 ( UPMF ) -Centre National de la Recherche Scientifique ( CNRS ), Department of Microbiology and Immunology, College of Medicine and Health Sciences-Sultan Qaboos University, European Molecular Biology Laboratory [Heidelberg] ( EMBL ), Department of Biostatistics, University of Michigan [Ann Arbor], Department of Radiation Oncology [Michigan] ( Radonc ), Department of Physics and Astronomy [Leicester], University of Leicester, Informatique, Biologie Intégrative et Systèmes Complexes ( IBISC ), Université d'Évry-Val-d'Essonne ( UEVE ) -Centre National de la Recherche Scientifique ( CNRS ), Institut für Meteorologie und Klimaforschung ( IMK ), Karlsruher Institut für Technologie ( KIT ), Physics Department [UNB], University of New Brunswick ( UNB ), Laboratoire Parole et Langage ( LPL ), Centre National de la Recherche Scientifique ( CNRS ) -Aix Marseille Université ( AMU ), Institut des Sciences Chimiques de Rennes ( ISCR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Ecole Nationale Supérieure de Chimie de Rennes-Institut National des Sciences Appliquées ( INSA ) -Centre National de la Recherche Scientifique ( CNRS ), Biogéosciences [Dijon] ( BGS ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Bioprojet, Laboratoire de Matériaux à Porosité Contrôlée ( LMPC ), Université de Haute-Alsace (UHA) Mulhouse - Colmar ( Université de Haute-Alsace (UHA) ) -Ecole Nationale Supérieure de Chimie de Mulhouse-Centre National de la Recherche Scientifique ( CNRS ), School of Information Engineering [USTB] ( SIE ), University of Science and Technology Beijing [Beijing] ( USTB ), Laboratory for Atmospheric and Space Physics [Boulder] ( LASP ), University of Colorado Boulder [Boulder], Department of Applied Mathematics [Sheffield], University of Sheffield [Sheffield], School of Mathematics and Statistics [Sheffield] ( SoMaS ), Laboratoire de Mécanique de Lille - FRE 3723 ( LML ), Université de Lille, Sciences et Technologies-Ecole Centrale de Lille-Centre National de la Recherche Scientifique ( CNRS ), Computer Science Department [UCLA] ( CSD ), University of California at Los Angeles [Los Angeles] ( UCLA ), Développement et évolution ( DE ), Université Paris-Sud - Paris 11 ( UP11 ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Biologie du Développement de Villefranche sur mer ( LBDV ), Laboratoire Pierre Aigrain ( LPA ), Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris ( FRDPENS ), Centre National de la Recherche Scientifique ( CNRS ) -École normale supérieure - Paris ( ENS Paris ) -Centre National de la Recherche Scientifique ( CNRS ) -École normale supérieure - Paris ( ENS Paris ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Department of Mathematics and Statistics [Mac Gill], McGill University, Departamento de Botánica [Comahue], Universidad nacional del Comahue, Bioénergétique Cellulaire et Pathologique ( BECP ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Environnements et Paléoenvironnements OCéaniques ( EPOC ), Observatoire aquitain des sciences de l'univers ( OASU ), Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers ( INSU - CNRS ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers ( INSU - CNRS ) -Centre National de la Recherche Scientifique ( CNRS ) -École pratique des hautes études ( EPHE ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Jacques Monod ( IJM ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratori Nazionali del Sud ( LNS ), National Institute for Nuclear Physics ( INFN ), Departament de Matemàtiques [Barcelona], Universitat Autònoma de Barcelona [Barcelona] ( UAB ), Max-Planck-Institut für Kohlenforschung (coal research), Institute of Oceanology [CAS] ( IOCAS ), National Chiao Tung University ( NCTU ), Department of Hydrology and Water Resources ( HWR ), University of Arizona, Centre for Educational Technology, Environment Department [York], University of York [York, UK], State Key Laboratory of Nuclear Physics and Technology ( SKL-NPT ), Peking University [Beijing], Department of Physics and Astronomy [Iowa City], University of Iowa [Iowa], NASA Ames Research Center ( ARC ), Department of Materials, Digital Language & Knowledge Contents Research Association ( DICORA ), Hankuk University of Foreign Studies, Department of Physics [Coventry], University of Warwick [Coventry], Space Science and Technology Department [Didcot] ( RAL Space ), STFC Rutherford Appleton Laboratory ( RAL ), Science and Technology Facilities Council ( STFC ) -Science and Technology Facilities Council ( STFC ), Institut de biologie et chimie des protéines [Lyon] ( IBCP ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), H M Nautical Almanac Office [RAL] ( HMNAO ), Rutherford Appleton Laboratory, United Kingdom Met Office [Exeter], University College of London [London] ( UCL ), Department of Pathology and Laboratory Medicine [UCLA], University of California at Los Angeles [Los Angeles] ( UCLA ) -School of Medicine, School of Earth and Environmental Sciences [Seoul] ( SEES ), Seoul National University [Seoul], Department of Chemistry, Seoul Women's University, MicroMachines Centre ( MMC ), Nanyang Technological University [Singapour], Regroupement Québécois sur les Matériaux de Pointe ( RQMP ), École Polytechnique de Montréal ( EPM ) -Université de Sherbrooke [Sherbrooke]-McGill University-Université de Montréal-Fonds Québécois de Recherche sur la Nature et les Technologies ( FQRNT ), Département de Physique [Montréal], Université de Montréal, School of Earth and Environment [Leeds] ( SEE ), Centre for Ecology and Hydrology ( CEH ), Natural Environment Research Council ( NERC ), Norwegian Institute for Water Research ( NIVA ), Norwegian Institute for Water Research, Stony Brook University [SUNY] (SBU), State University of New York (SUNY)-State University of New York (SUNY), Astronomy Unit [London] (AU), Queen Mary University of London (QMUL), Commonwealth Scientific and Industrial Research Organisation Energy Technology (CSIRO Energy Technology), Commonwealth Scientific and Industrial Research Organisation [Canberra] (CSIRO), Department of Biochemistry and Molecular Biology [Houston], The University of Texas Medical School at Houston, Mathematical Institute [Oxford] (MI), University of Oxford, Centre for the Analysis of Time Series (CATS), London School of Economics and Political Science (LSE), Thomas Jefferson National Accelerator Facility (Jefferson Lab), Laboratoire Énergies et Mécanique Théorique et Appliquée (LEMTA ), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Evolution, Génomes et Spéciation (LEGS), Centre National de la Recherche Scientifique (CNRS), University of Illinois System-University of Illinois System, Department of Electrical and Computer Engineering [Portland] (ECE), Portland State University [Portland] (PSU), Saint-Gobain, Institute for Animal Health (IAH), Biotechnology and Biological Sciences Research Council (BBSRC), Chinese Academy of Sciences [Changchun Branch] (CAS), Ipsen Inc. [Milford] (Ipsen), University of California [Berkeley] (UC Berkeley), University of California (UC)-University of California (UC), Institute for Climate and Atmospheric Science [Leeds] (ICAS), School of Earth and Environment [Leeds] (SEE), University of Leeds-University of Leeds, Chung-Ang University (CAU), Antarctic Climate and Ecosystems Cooperative Research Centre (ACE-CRC), Institute of Aerodynamics and Fluid Mechanics (AER), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Mer et santé (MS), Station biologique de Roscoff [Roscoff] (SBR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), National Physical Laboratory [Teddington] (NPL), International Research Institute for Climate and Society (IRI), Macaulay Institute, University of Cambridge [UK] (CAM), Queen's University [Kingston, Canada], Leslie Hill Institute for Plant Conservation (PCU), Istituto per la Microelettronica e Microsistemi [Catania] (IMM), National Research Council of Italy | Consiglio Nazionale delle Ricerche (CNR), Laboratoire d'Acoustique de l'Université du Mans (LAUM), Le Mans Université (UM)-Centre National de la Recherche Scientifique (CNRS), Interactive Systems Labs (ISL), Carnegie Mellon University [Pittsburgh] (CMU), Dalian Institute of Chemical Physics (DICP), Architectures, Languages and Compilers to Harness the End of Moore Years (ALCHEMY), Laboratoire de Recherche en Informatique (LRI), Université Paris-Sud - Paris 11 (UP11)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Clean Air Task Force (CATF), Indian Space Research Organisation (ISRO), Centre d'études et de recherches appliquées à la gestion (CERAG), Université Pierre Mendès France - Grenoble 2 (UPMF)-Centre National de la Recherche Scientifique (CNRS), Sultan Qaboos University (SQU)-College of Medicine and Health Sciences [Baylor], Baylor University-Baylor University, European Molecular Biology Laboratory [Heidelberg] (EMBL), University of Michigan System-University of Michigan System, Department of Radiation Oncology [Michigan] (Radonc), Informatique, Biologie Intégrative et Systèmes Complexes (IBISC), Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Institute for Meteorology and Climate Research (IMK), Karlsruhe Institute of Technology (KIT), University of New Brunswick (UNB), Laboratoire Parole et Langage (LPL), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences Chimiques de Rennes (ISCR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Biogéosciences [UMR 6282] (BGS), Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Matériaux à Porosité Contrôlée (LMPC), Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS), School of Information Engineering [USTB] (SIE), University of Science and Technology Beijing [Beijing] (USTB), Laboratory for Atmospheric and Space Physics [Boulder] (LASP), University of Colorado [Boulder], School of Mathematics and Statistics [Sheffield] (SoMaS), Laboratoire de Mécanique de Lille - FRE 3723 (LML), Université de Lille, Sciences et Technologies-Centrale Lille-Centre National de la Recherche Scientifique (CNRS), Computer Science Department [UCLA] (CSD), University of California [Los Angeles] (UCLA), Développement et évolution (DE), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biologie du Développement de Villefranche sur mer (LBDV), Observatoire océanologique de Villefranche-sur-mer (OOVM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Pierre Aigrain (LPA), Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Department of Mathematics and Statistics [Montréal], McGill University = Université McGill [Montréal, Canada], Departamento de Botánica [Bariloche], Centro Regional Universitario Bariloche [Bariloche] (CRUB), Universidad Nacional del Comahue [Neuquén] (UNCOMA)-Universidad Nacional del Comahue [Neuquén] (UNCOMA), Bioénergétique Cellulaire et Pathologique (BECP), Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Environnements et Paléoenvironnements OCéaniques (EPOC), Observatoire aquitain des sciences de l'univers (OASU), Université Sciences et Technologies - Bordeaux 1 (UB)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1 (UB)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Laboratori Nazionali del Sud (LNS), Istituto Nazionale di Fisica Nucleare (INFN), Departament de Matemàtiques [Barcelona] (UAB), Universitat Autònoma de Barcelona (UAB), Max-Planck-Institut für Kohlenforschung (Coal Research), Max-Planck-Gesellschaft, CAS Institute of Oceanology (IOCAS), Chinese Academy of Sciences [Beijing] (CAS), National Chiao Tung University (NCTU), Department of Hydrology and Water Resources (HWR), State Key Laboratory of Nuclear Physics and Technology (SKL-NPT), University of Iowa [Iowa City], NASA Ames Research Center (ARC), Digital Language & Knowledge Contents Research Association (DICORA), Space Science and Technology Department [Didcot] (RAL Space), STFC Rutherford Appleton Laboratory (RAL), Science and Technology Facilities Council (STFC)-Science and Technology Facilities Council (STFC), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), H M Nautical Almanac Office [RAL] (HMNAO), University College of London [London] (UCL), University of California (UC)-University of California (UC)-School of Medicine, School of Earth and Environmental Sciences [Seoul] (SEES), Seoul National University [Seoul] (SNU), MicroMachines Centre (MMC), Regroupement Québécois sur les Matériaux de Pointe (RQMP), École Polytechnique de Montréal (EPM)-Université de Sherbrooke (UdeS)-McGill University = Université McGill [Montréal, Canada]-Université de Montréal (UdeM)-Fonds Québécois de Recherche sur la Nature et les Technologies (FQRNT), Université de Montréal (UdeM), Centre for Ecology and Hydrology (CEH), Natural Environment Research Council (NERC), Norwegian Institute for Water Research (NIVA), SEA URCHIN GENOME SEQUENCING CONSORTIUM, SODERGREN E, WEINSTOCK GM, DAVIDSON EH, CAMERON RA, GIBBS RA, ANGERER RC, ANGERER LM, ARNONE MI, BURGESS DR, BURKE RD, COFFMAN JA, DEAN M, ELPHICK MR, ETTENSOHN CA, FOLTZ KR, HAMDOUN A, HYNES RO, KLEIN WH, MARZLUFF W, MCCLAY DR, MORRIS RL, MUSHEGIAN A, RAST JP, SMITH LC, THORNDYKE MC, VACQUIER VD, WESSEL GM, WRAY G, ZHANG L, ELSIK CG, ERMOLAEVA O, HLAVINA W, HOFMANN G, KITTS P, LANDRUM MJ, MACKEY AJ, MAGLOTT D, PANOPOULOU G, POUSTKA AJ, PRUITT K, SAPOJNIKOV V, SONG X, SOUVOROV A, SOLOVYEV V, WEI Z, WHITTAKER CA, WORLEY K, DURBIN KJ, SHEN Y, FEDRIGO O, GARFIELD D, HAYGOOD R, PRIMUS A, SATIJA R, SEVERSON T, GONZALEZ-GARAY ML, JACKSON AR, MILOSAVLJEVIC A, TONG M, KILLIAN CE, LIVINGSTON BT, WILT FH, ADAMS N, BELLE R, CARBONNEAU S, CHEUNG R, CORMIER P, COSSON B, CROCE J, FERNANDEZ-GUERRA A, GENEVIERE AM, GOEL M, KELKAR H, MORALES J, MULNER-LORILLON O, ROBERTSON AJ, GOLDSTONE JV, COLE B, EPEL D, GOLD B, HAHN ME, HOWARD-ASHBY M, SCALLY M, STEGEMAN JJ, ALLGOOD EL, COOL J, JUDKINS KM, MCCAFFERTY SS, MUSANTE AM, OBAR RA, RAWSON AP, ROSSETTI BJ, GIBBONS IR, HOFFMAN MP, LEONE A, ISTRAIL S, MATERNA SC, SAMANTA MP, STOLC V, TONGPRASIT W, TU Q, BERGERON KF, BRANDHORST BP, WHITTLE J, BERNEY K, BOTTJER DJ, CALESTANI C, PETERSON K, CHOW E, YUAN QA, ELHAIK E, GRAUR D, REESE JT, BOSDET I, HEESUN S, MARRA MA, SCHEIN J, ANDERSON MK, BROCKTON V, BUCKLEY KM, COHEN AH, FUGMANN SD, HIBINO T, LOZA-COLL M, MAJESKE AJ, MESSIER C, NAIR SV, PANCER Z, TERWILLIGER DP, AGCA C, ARBOLEDA E, CHEN N, CHURCHER AM, HALLBOOK F, HUMPHREY GW, IDRIS MM, KIYAMA T, LIANG S, MELLOTT D, MU X, MURRAY G, OLINSKI RP, RAIBLE F, ROWE M, TAYLOR JS, TESSMAR-RAIBLE K, WANG D, WILSON KH, YAGUCHI S, GAASTERLAND T, GALINDO BE, GUNARATNE HJ, JULIANO C, KINUKAWA M, MOY GW, NEILL AT, NOMURA M, RAISCH M, READE A, ROUX MM, SONG JL, SU YH, TOWNLEY IK, VORONINA E, WONG JL, AMORE G, BRANNO M, BROWN ER, CAVALIERI, V, DUBOC V, DULOQUIN L, FLYTZANIS C, GACHE C, LAPRAZ F, LEPAGE T, LOCASCIO A, MART, University of California-University of California, Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Consiglio Nazionale delle Ricerche (CNR), Centre National de la Recherche Scientifique (CNRS)-Le Mans Université (UM), Centre National de la Recherche Scientifique (CNRS)-Université Pierre Mendès France - Grenoble 2 (UPMF), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Biogéosciences [UMR 6282] [Dijon] (BGS), Centre National de la Recherche Scientifique (CNRS)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Ecole Nationale Supérieure de Chimie de Mulhouse-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-École pratique des hautes études (EPHE), University of California-University of California-School of Medicine, Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Université de Lille, Sciences et Technologies-Centre National de la Recherche Scientifique (CNRS)-Centrale Lille, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF), University of Manchester Institute of Science and Technology (UMIST), Condensed Matter Physics and Materials Science Department, Brookhaven National Laboratory, Brookhaven National Laboratory [Upton, NY] (BNL), UT-Battelle, LLC-Stony Brook University [SUNY] (SBU), State University of New York (SUNY)-State University of New York (SUNY)-U.S. Department of Energy [Washington] (DOE)-UT-Battelle, LLC-Stony Brook University [SUNY] (SBU), State University of New York (SUNY)-State University of New York (SUNY)-U.S. Department of Energy [Washington] (DOE), Baylor College of Medicine (BCM), Baylor University, Laboratoire de Traitement de l'Information Medicale (LaTIM), Université européenne de Bretagne - European University of Brittany (UEB)-Université de Brest (UBO)-Télécom Bretagne-Institut Mines-Télécom [Paris] (IMT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Laboratoire de Modélisation et Simulation Multi Echelle (MSME), Université Paris-Est Marne-la-Vallée (UPEM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Duke University [Durham], Instituto Andaluz de Geofísica y Prevención de Desastres Sísmicos [Granada] (IAGPDS), Universidad de Granada (UGR), Laboratoire d'Ingénierie des Matériaux de Bretagne (LIMATB), Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Université de Brest (UBO), University of New South Wales [Sydney] (UNSW), Celera Genomics (CRA), Celera Genomics, Paléobiodiversité et paléoenvironnements, Muséum national d'Histoire naturelle (MNHN)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Roma Tor Vergata [Roma], Unité de recherches forestières (BORDX PIERR UR ), Institut National de la Recherche Agronomique (INRA), Deptartment of Neuroscience, Uppsala University, State Key Laboratory of Palaeobiology and Stratigraphy, Nanjing Institute of Geology and Palaeontology (NIGPAS-CAS), Chinese Academy of Sciences [Nanjing Branch]-Chinese Academy of Sciences [Nanjing Branch], Institut Méditerranéen d'Ecologie et de Paléoécologie (IMEP), Université Paul Cézanne - Aix-Marseille 3-Université de Provence - Aix-Marseille 1-Avignon Université (AU)-Centre National de la Recherche Scientifique (CNRS), Key Laboratory of Ocean Circulation and Waves, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China, Université Paris Diderot - Paris 7 (UPD7), Department of Physical and Environmental Sciences [Toronto], University of Toronto at Scarborough, inconnu temporaire UPEMLV, Inconnu, Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Department of Atmospheric Sciences [Seattle], University of Washington [Seattle], National Institute of Advanced Industrial Science and Technology (AIST), Department of Pharmacy, Università degli studi di Genova = University of Genoa (UniGe), Interdisciplinary Arts and Sciences Department, St. Vincent's Hospital, Sydney, Laboratoire des Sciences de l'Environnement Marin (LEMAR) (LEMAR), Institut de Recherche pour le Développement (IRD)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Brest (UBO)-Institut Universitaire Européen de la Mer (IUEM), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Department of Electrical Engineering (DEE-POSTECH), Pohang University of Science and Technology (POSTECH), Centre Suisse d'Electronique et de Microtechnique SA [Neuchatel] (CSEM), Centre Suisse d'Electronique et Microtechnique SA (CSEM), Human Genome Sequencing Center [Houston] (HGSC), Brookhaven National Laboratory, Meteorological Service of Canada, 4905 Dufferin Street, Université européenne de Bretagne - European University of Brittany (UEB)-Télécom Bretagne-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Mines-Télécom [Paris] (IMT), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Université Paris-Est Marne-la-Vallée (UPEM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherches Forestières, Department of Physical and Environmental Sciences, University of Toronto [Scarborough, Canada], National Institute for Nuclear Physics (INFN), University of Genoa (UNIGE), Institut de Recherche pour le Développement (IRD)-Institut Universitaire Européen de la Mer (IUEM), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Université de Brest (UBO)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS), Universidad de Granada = University of Granada (UGR), Laboratoire d'Energétique et de Mécanique Théorique Appliquée (LEMTA ), Technische Universität München [München] (TUM), Queen's University [Kingston], Centre National de la Recherche Scientifique (CNRS)-Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Grenoble Alpes (UGA), Institut für Meteorologie und Klimaforschung (IMK), Karlsruher Institut für Technologie (KIT), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Rennes-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES), Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Sciences et Technologies-Ecole Centrale de Lille-Université de Lille, Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-École pratique des hautes études (EPHE)-Centre National de la Recherche Scientifique (CNRS), Universitat Autònoma de Barcelona [Barcelona] (UAB), École Polytechnique de Montréal (EPM)-Université de Sherbrooke [Sherbrooke]-Université de Montréal [Montréal]-McGill University-Fonds Québécois de Recherche sur la Nature et les Technologies (FQRNT), Université de Montréal [Montréal], U.S. Department of Energy [Washington] (DOE)-UT-Battelle, LLC-Stony Brook University [SUNY] (SBU), Université de Bretagne Sud (UBS)-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Université de Brest (UBO)-Université de Brest (UBO), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Paul Cézanne - Aix-Marseille 3-Centre National de la Recherche Scientifique (CNRS)-Avignon Université (AU)-Université de Provence - Aix-Marseille 1, Institut Universitaire Européen de la Mer (IUEM), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS)-Université de Brest (UBO), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université de Lille, Sciences et Technologies-Ecole Centrale de Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Paris (ENS Paris), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, MESH: Signal Transduction, MESH: Sequence Analysis, DNA, MESH : Transcription Factors, MESH : Calcification, Physiologic, Genome, MESH : Proteins, 0302 clinical medicine, MESH : Embryonic Development, MESH: Gene Expression Regulation, Developmental, Innate, MESH: Embryonic Development, Developmental, Nervous System Physiological Phenomena, MESH: Animals, MESH: Proteins, [SDV.BDD]Life Sciences [q-bio]/Development Biology, Complement Activation, ComputingMilieux_MISCELLANEOUS, MESH: Evolution, Molecular, MESH : Strongylocentrotus purpuratus, Genetics, 0303 health sciences, MESH: Nervous System Physiological Phenomena, Multidisciplinary, biology, Medicine (all), MESH: Immunologic Factors, Gene Expression Regulation, Developmental, Genome project, MESH: Transcription Factors, MESH : Immunity, Innate, MESH : Complement Activation, MESH: Genes, Bacterial artificial chromosome (BAC)DeuterostomesStrongylocentrotus purpuratusVertebrate innovations, Echinoderm, MESH : Nervous System Physiological Phenomena, embryonic structures, MESH: Cell Adhesion Molecules, MESH : Genes, MESH: Immunity, Innate, Sequence Analysis, Signal Transduction, MESH: Computational Biology, Genome evolution, MESH: Complement Activation, Sequence analysis, Evolution, MESH: Strongylocentrotus purpuratus, MESH : Male, Embryonic Development, MESH : Immunologic Factors, Article, MESH: Calcification, Physiologic, Calcification, MESH : Cell Adhesion Molecules, Evolution, Molecular, 03 medical and health sciences, Calcification, Physiologic, Animals, Immunologic Factors, MESH: Genome, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH : Evolution, Molecular, Physiologic, Gene, Strongylocentrotus purpuratus, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, MESH : Signal Transduction, Bacterial artificial chromosome, Immunity, Molecular, Computational Biology, Proteins, Cell Adhesion Molecules, Genes, Immunity, Innate, Transcription Factors, Sequence Analysis, DNA, DNA, biology.organism_classification, MESH: Male, Gene Expression Regulation, MESH : Animals, MESH : Gene Expression Regulation, Developmental, MESH : Genome, 030217 neurology & neurosurgery, MESH : Computational Biology, MESH : Sequence Analysis, DNA
Abstract: We report the sequence and analysis of the 814-megabase genome of the sea urchin Strongylocentrotus purpuratus , a model for developmental and systems biology. The sequencing strategy combined whole-genome shotgun and bacterial artificial chromosome (BAC) sequences. This use of BAC clones, aided by a pooling strategy, overcame difficulties associated with high heterozygosity of the genome. The genome encodes about 23,300 genes, including many previously thought to be vertebrate innovations or known only outside the deuterostomes. This echinoderm genome provides an evolutionary outgroup for the chordates and yields insights into the evolution of deuterostomes.
Published: 2006
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29. [An increase in intracellular free calcium controls the expression of an arginine N-methyl-transferase involved in neural determination in amphibian embryo]

Author: Néant, Isabelle, Leclerc, Catherine, Batut, Julie, Vandel, Laurence, Moreau, Marc, Centre de biologie du développement (CBD), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre de Biologie Intégrative (CBI), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre de biologie du développement ( CBD ), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques ( LCBPT - UMR 8601 ), and Université Paris Descartes - Paris 5 ( UPD5 ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: MESH: Cell Differentiation, MESH: Enzyme Induction, MESH : Transcription Factors, MESH: Egtazic Acid, MESH: Bone Morphogenetic Proteins, MESH: Carrier Proteins, MESH: Bone Morphogenetic Protein Receptors, MESH: Calcium Signaling, MESH: Chelating Agents, MESH : Blastula, MESH: Caffeine, MESH : Bone Morphogenetic Protein Receptors, MESH : Bone Morphogenetic Proteins, MESH : Calcium Signaling, MESH: Xenopus laevis, MESH: Gastrula, MESH : Gastrula, MESH: Homeodomain Proteins, MESH: Methyltransferases, MESH : Xenopus laevis, MESH : Chelating Agents, MESH: Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH : Homeodomain Proteins, MESH: Blastula, MESH : Calcium, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Xenopus Proteins, MESH : Caffeine, MESH : Methyltransferases, MESH : Organ Culture Techniques, MESH : Ectoderm, MESH: Nervous System, MESH : Enzyme Induction, MESH : Xenopus Proteins, MESH : Egtazic Acid, MESH: Transcription Factors, MESH: Organ Culture Techniques, MESH: Calcium, MESH : Nervous System, MESH : Animals, MESH : Carrier Proteins, MESH : Cell Differentiation, MESH: Ectoderm
Published: 2006

30. Expression of Pitx2 in stromal cells is required for normal hematopoiesis

Author: Bernard G. Forget, Nicole Navarro, Anne Dubart-Kupperschmitt, Georges Uzan, Brigitte Izac, Philip J. Gage, Cécile Kerdudo, Aurélie Kieusseian, Philippe E. Mangeot, Jalila Chagraoui, Garcia, Marie, Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Human Genetics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Medicine/Genetics, Yale School of Medicine [New Haven, Connecticut] (YSM), Ontogenese de l'Hematopoiese, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Yale University School of Medicine, Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), Yale School of Medicine, and Université Paris-Sud - Paris 11 (UP11) - Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: [SDV.BIO]Life Sciences [q-bio]/Biotechnology, MESH : Transcription Factors, MESH: Hematopoiesis, MESH : RNA, Small Interfering, Biochemistry, MESH: Mice, Knockout, Mice, 0302 clinical medicine, MESH: RNA, Small Interfering, MESH: Gene Expression Regulation, Developmental, MESH: Animals, MESH : Homeodomain Proteins, RNA, Small Interfering, [INFO.INFO-BT]Computer Science [cs]/Biotechnology, Cells, Cultured, MESH: Lentivirus, Mice, Knockout, 0303 health sciences, PITX2, Stem Cells, Homozygote, Gene Expression Regulation, Developmental, Nuclear Proteins, Hematology, MESH: Transcription Factors, MESH : Fetus, Cell biology, Haematopoiesis, medicine.anatomical_structure, MESH : Lentivirus, Liver, 030220 oncology & carcinogenesis, MESH : Stem Cells, MESH : Transfection, MESH : Colony-Forming Units Assay, MESH: Cells, Cultured, MESH: Homozygote, congenital, hereditary, and neonatal diseases and abnormalities, Stromal cell, Ratón, Immunology, MESH : Mice, Inbred C57BL, MESH: Stem Cells, Biology, Transfection, Colony-Forming Units Assay, 03 medical and health sciences, Fetus, MESH : Homozygote, stomatognathic system, MESH: Mice, Inbred C57BL, MESH : Cells, Cultured, MESH : Mice, MESH: Homeodomain Proteins, Lymph node stromal cell, medicine, Animals, MESH: Colony-Forming Units Assay, Progenitor cell, MESH: Mice, 030304 developmental biology, Homeodomain Proteins, MESH: Transfection, Lentivirus, MESH : Nuclear Proteins, MESH : Liver, MESH: Fetus, Cell Biology, Hematopoiesis, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, Mice, Inbred C57BL, MESH : Hematopoiesis, stomatognathic diseases, [INFO.INFO-BT] Computer Science [cs]/Biotechnology, MESH : Stromal Cells, MESH : Mice, Knockout, Bone marrow, MESH : Animals, MESH : Gene Expression Regulation, Developmental, sense organs, Stromal Cells, MESH: Stromal Cells, MESH: Nuclear Proteins, Transcription Factors, MESH: Liver
Abstract: Although the expression of Pitx2, a bicoid family homeodomain transcription factor, is highly regulated during hematopoiesis, its function during this process was not documented; we thus studied hematopoiesis in Pitx2-null mice. We found that Pitx2–/– embryos display hypoplastic livers with reduced numbers of hematopoietic cells, but these cells had normal hematopoietic potential, as evidenced by colony-forming assays, immature progenitor cell assays, and long-term repopulation assays. Because the microenvironment is also crucial to the development of normal hematopoiesis, we established Pitx2–/– and Pitx2+/+ stromas from fetal liver and studied their hematopoietic supportive capacity. We showed that the frequency of cobblestone area-forming cells was 4-fold decreased when using Pitx2–/– stromal cells compared with Pitx2+/+ stromal cells, whatever the Pitx2 genotype of hematopoietic cells tested in this assay. This defect was rescued by expression of Pitx2 into Pitx2–/– fetal liver stromal cells, demonstrating a major and direct role of Pitx2 in the hematopoietic supportive capacity of fetal liver stroma. Finally, we showed a reduced capacity of MS5 stromal cells expressing Pitx2 RNAi to support human hematopoiesis. Altogether these data showed that Pitx2 has major functions in the hematopoietic supportive capacity of fetal liver and adult bone marrow stromal cells.
Published: 2006
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31. Tsg101 and Alix interact with murine leukemia virus Gag and cooperate with Nedd4 ubiquitin ligases during budding

Author: Christine Chatellard-Causse, Christina Pescia, Edouard Bertrand, Rémy Sadoul, Eugenia Basyuk, Carolina Segura-Morales, Institut de Génétique Moléculaire de Montpellier ( IGMM ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Neurodegenerescence et Plasticite, Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Fraboulet, Sandrine, and Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH : Cell Line, MESH : Transcription Factors, Nedd4 Ubiquitin Protein Ligases, viruses, MESH : Gene Products, gag, NEDD4, MESH: Calcium-Binding Proteins, Virus Replication, Biochemistry, Mice, Ubiquitin, MESH : Calcium-Binding Proteins, Murine leukemia virus, TSG101, MESH: Animals, MESH : Ubiquitin, 0303 health sciences, biology, MESH : Rats, 030302 biochemistry & molecular biology, MESH: Leukemia Virus, Murine, MESH: Transcription Factors, MESH : Mutagenesis, Site-Directed, DNA-Binding Proteins, Leukemia Virus, Murine, MESH : Virus Replication, MESH: Mutagenesis, Site-Directed, MESH: Gene Products, gag, MESH : DNA-Binding Proteins, MESH : Transfection, MESH : Carrier Proteins, MESH : Leukemia Virus, Murine, MESH: Ubiquitin, MESH: Rats, Endosome, Ubiquitin-Protein Ligases, Gene Products, gag, MESH: Carrier Proteins, macromolecular substances, Transfection, Cell Line, 03 medical and health sciences, MESH : Mice, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Binding site, MESH: Mice, Molecular Biology, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, Binding Sites, MESH: Humans, Endosomal Sorting Complexes Required for Transport, MESH: Transfection, Calcium-Binding Proteins, MESH: Virus Replication, MESH : Humans, Cell Biology, biology.organism_classification, MESH: Ubiquitin-Protein Ligases, Virology, Rats, MESH: Cell Line, MESH: Binding Sites, Viral replication, Mutagenesis, Site-Directed, biology.protein, MESH : Animals, MESH : Ubiquitin-Protein Ligases, Carrier Proteins, MESH: DNA-Binding Proteins, MESH : Binding Sites, Transcription Factors
Abstract: International audience; Retroviruses use endosomal machinery to bud out of infected cells, and various Gag proteins recruit this machinery by interacting with either of three cellular factors as follows: ubiquitin ligases of the Nedd4 family, Tsg101, or Alix/Aip1. Here we show that the murine leukemia virus Gag has the unique ability to interact with all three factors. Small interfering RNAs against Tsg101 or Alix and dominant-negative forms of Nedd4 can all reduce production of virus-like particles. However, inactivating the Nedd4-binding site abolishes budding, whereas disrupting Tsg101 or Alix binding has milder effects. Nedd4 ubiquitin ligases are therefore essential, and Tsg101 and Alix play auxiliary roles. Most interestingly, overexpression of Alix can stimulate the release of Gag, and this occurs independently of most Alix partners Tsg101, Cin85, Alg-2, and endophilins. In addition, Gag mutants that do not bind Tsg101 or Alix concentrate on late endosomes and become very sensitive to dominant-negative forms of Nedd4 that do not conjugate ubiquitin. This suggests that the direct interaction of Gag with Tsg101 and Alix favors budding from the plasma membrane and relieves a requirement for ubiquitination by Nedd4.1. Other Nedd4-dependent Gag proteins also contain binding sites for Tsg101 or Alix, suggesting that this could be a common feature of retroviruses.
Published: 2005
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32. Role of transcription factor KLF11 and its diabetes-associated gene variants in pancreatic beta cell function

Author: Geesje M. Dallinga-Thie, Danielle Melloul, Raul Urrutia, Vered Ashkenazi-Katalan, Guillaume Charpentier, Torben Hansen, Oluf Pedersen, Nicolas Bakaher, Yamina Benmezroua, Emmanuelle Durand, Marc Prentki, Serge Hercberg, Karine Clément, Tiffany Cook, Martine Vaxillaire, Marie-Aline Charles, Valérie Delannoy, Yasmin H. Hamid, Bernadette Neve, Erik Joly, Nicole Helbecque, Christian Dina, Emmanuel Vaillant, Pilar Galan, Martin E. Fernandez-Zapico, Philippe Froguel, Hans Jansen, Institut de biologie de Lille - UMS 3702 (IBL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Mayo Clinic [Rochester], Hadassah Hebrew University Medical Center [Jerusalem], Génétique des maladies multifactorielles (GMM), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Steno Diabetes Center and Hagedorn Research Institute, Departement /u563 : Immunologie et Maladies infectieuses, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Réponse immunitaire et complexe majeur d'histocompatibilité (U395), Institut National de la Santé et de la Recherche Médicale (INSERM), Departement /u563 : Lipoproteines et Mediateurs Lipidiques, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Recherche en épidémiologie et biostatistique, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Systèmes Macromoléculaires et Physiopathologie Humaine (SMPH), BIOMERIEUX-Centre National de la Recherche Scientifique (CNRS), Epidémiologie cardiovasculaire et métabolique, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Déterminants Biologiques et Comportementaux des Obésités, EA3502-Hôtel-Dieu-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Pierre et Marie Curie - Paris 6 (UPMC), Service de nutrition, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital de l'Hôtel-Dieu, Nutrition et obésité : approches génétique et transcriptomique, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR58-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de nutrition, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu, Unité de Recherche en Epidémiologie Nutritionnelle (UREN), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Epidémiologie des maladies chroniques: impact des intéractions gène environnement sur la santé des populations, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Sud Francilien, CH Evry-Corbeil, Hopital Notre-Dame, Steno Diabetes Center, Section of Genomic Medicine, Imperial College London, Genome Centre, Imperial College London-Hammersmith campus, Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), The Functional Immunogenetics Laboratory, The Babraham Institute, Institut de Chimie de la Matière Condensée de Bordeaux (ICMCB), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Développement artériel, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Mercator Océan, Société Civile CNRS Ifremer IRD Météo-France SHOM, EA3502-Hôtel-Dieu-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Pierre et Marie Curie - Paris 6 (UPMC), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital de l'Hôtel-Dieu, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôtel-Dieu, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Cité (USPC)-Université Paris 13 (UP13)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut National de la Recherche Agronomique (INRA), Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Service de diabétologie, CH Evry-Corbeil-CH Evry-Corbeil, Service d'endocrinologie et diabetologie, Hôpital de Corbeil-ESsonnes, Génétique des maladies multifactorielles ( GMM ), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique ( CNRS ), Centre de Physiopathologie Toulouse Purpan (ex IFR 30 et IFR 150), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR30-IFR150-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR30-IFR150-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Réponse immunitaire et complexe majeur d'histocompatibilité ( U395 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ), Physique, Université de Lille, Sciences Humaines et Sociales, Institut de Chimie de la Matière Condensée de Bordeaux ( ICMCB ), Centre National de la Recherche Scientifique ( CNRS ) -Université de Bordeaux ( UB ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Systèmes Macromoléculaires et Physiopathologie Humaine ( SMPH ), BIOMERIEUX-Centre National de la Recherche Scientifique ( CNRS ), EA3502-Hôtel-Dieu-Assistance publique - Hôpitaux de Paris (AP-HP)-Université Pierre et Marie Curie - Paris 6 ( UPMC ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital de l'Hôtel-Dieu, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -IFR58-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôtel-Dieu, Unité de Recherche en Epidémiologie Nutritionnelle ( UREN ), Institut National de la Recherche Agronomique ( INRA ) -Conservatoire National des Arts et Métiers [CNAM] ( CNAM ) -Université Paris 13 ( UP13 ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Réseau International des Instituts Pasteur ( RIIP ) -Réseau International des Instituts Pasteur ( RIIP ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Réseau International des Instituts Pasteur ( RIIP ) -Réseau International des Instituts Pasteur ( RIIP ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lille, Droit et Santé, Department of Applied Physics ( GU ), State University of Ghent, Vascular Medicine, Experimental Vascular Medicine, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-EA3502, Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université (HESAM)-HESAM Université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Internal Medicine, Clinical Chemistry, Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôtel-Dieu-EA3502, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: medicine.medical_treatment, Cell Cycle Proteins, MESH: Base Sequence, 0302 clinical medicine, MESH : Cell Cycle Proteins, Human genetics, Insulin, MESH: Gene Components, [ SDV.GEN.GH ] Life Sciences [q-bio]/Genetics/Human genetics, Regulation of gene expression, MESH: Chromatin Immunoprecipitation, 0303 health sciences, Base Composition, MESH : Gene Expression Regulation, MESH: Transcription Factors, MESH: Case-Control Studies, 3. Good health, Pedigree, MESH: Promoter Regions (Genetics), MESH: Repressor Proteins, Promoter Regions (Genetics), Pancreas, Type 2, MESH: Diabetes Mellitus, Type 2, MESH : Case-Control Studies, MESH: Pedigree, Molecular Sequence Data, MESH: Sequence Alignment, MESH: Insulin, 03 medical and health sciences, Islets of Langerhans, MESH: Cell Cycle Proteins, SDG 3 - Good Health and Well-being, Genetic, MESH: Polymorphism, Genetic, Diabetes Mellitus, Humans, MESH : Islets of Langerhans, Polymorphism, Polymorphism, Genetic, MESH: Humans, MESH: Molecular Sequence Data, MESH: Islets of Langerhans, MESH : Humans, DNA, medicine.disease, MESH : Promoter Regions (Genetics), Diabetes Mellitus, Type 2, Case-Control Studies, MESH: Luciferases, Apoptosis Regulatory Proteins, MESH : Sequence Analysis, DNA, Transcription Factors, MESH: Sequence Analysis, DNA, MESH : Molecular Sequence Data, MESH : Transcription Factors, MESH : Polymorphism, Genetic, MESH : Insulin, Type 2 diabetes, MESH : Diabetes Mellitus, Type 2, Promoter Regions, Genetic, Luciferases, Multidisciplinary, MESH : Sequence Alignment, Biological Sciences, MESH : Gene Components, MESH: Gene Expression Regulation, Europe, medicine.anatomical_structure, Gene Components, Base Sequence, Chromatin Immunoprecipitation, Gene Expression Regulation, Repressor Proteins, Sequence Alignment, Sequence Analysis, Beta cell, MESH : Repressor Proteins, MESH : Europe, 030209 endocrinology & metabolism, Biology, MESH : Base Composition, Génétique humaine, MESH : Chromatin Immunoprecipitation, MESH: Base Composition, Diabetes mellitus, medicine, Transcription factor, 030304 developmental biology, MESH : Luciferases, Type 2 Diabetes Mellitus, Sequence Analysis, DNA, Molecular biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, MESH : Pedigree, MESH : Base Sequence, MESH: Europe
Abstract: KLF11 (TIEG2) is a pancreas-enriched transcription factor that has elicited significant attention because of its role as negative regulator of exocrine cell growth in vitro and in vivo . However, its functional role in the endocrine pancreas remains to be established. Here, we report, for the first time, to our knowledge, the characterization of KLF11 as a glucose-inducible regulator of the insulin gene. A combination of random oligonucleotide binding, EMSA, luciferase reporter, and chromatin immunoprecipitation assays shows that KLF11 binds to the insulin promoter and regulates its activity in beta cells. Genetic analysis of the KLF11 gene revealed two rare variants (Ala347Ser and Thr220Met) that segregate with diabetes in families with early-onset type 2 diabetes, and significantly impair its transcriptional activity. In addition, analysis of 1,696 type 2 diabetes mellitus and 1,776 normoglycemic subjects show a frequent polymorphic Gln62Arg variant that significantly associates with type 2 diabetes mellitus in North European populations (OR = 1.29, P = 0.00033). Moreover, this variant alters the corepressor mSin3A-binding activity of KLF11, impairs the activation of the insulin promoter and shows lower levels of insulin expression in pancreatic beta cells. In addition, subjects carrying the Gln62Arg allele show decreased plasma insulin after an oral glucose challenge. Interestingly, all three nonsynonymous KLF11 variants show increased repression of the catalase 1 promoter, suggesting a role in free radical clearance that may render beta cells more sensitive to oxidative stress. Thus, both functional and genetic analyses reveal that KLF11 plays a role in the regulation of pancreatic beta cell physiology, and its variants may contribute to the development of diabetes.
Published: 2005
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33. Expression patterns of the coe/ebf transcription factor genes during chicken and mouse limb development

Author: Alain Vincent, Sébastien Mella, Dominique Morello, Michèle Crozatier, Cathy Soula, Centre de biologie du développement (CBD), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Laboratoire Bordelais de Recherche en Informatique (LaBRI), Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Université Sciences et Technologies - Bordeaux 1-Université Bordeaux Segalen - Bordeaux 2, Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Anatomopathologie Haut-Lévêque (ANATOMOPATHOLOGIE), CHU, Clinical Neurology Oxford (CLINICAL NEUROLOGY), Hospital, Departement /u661 : Endocrinologie, Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de synthèse organique (DCSO), École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), FLAveur, VIsion et Comportement du consommateur (FLAVIC), Etablissement National d'Enseignement Supérieur Agronomique de Dijon (ENESAD)-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB), Centre de biologie du développement ( CBD ), Université Paul Sabatier - Toulouse 3 ( UPS ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire Bordelais de Recherche en Informatique ( LaBRI ), Centre National de la Recherche Scientifique ( CNRS ) -École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Université Sciences et Technologies - Bordeaux 1-Université Bordeaux Segalen - Bordeaux 2, Institut de Génomique Fonctionnelle ( IGF ), Centre National de la Recherche Scientifique ( CNRS ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Montpellier 1 ( UM1 ) -Université de Montpellier ( UM ), Anatomopathologie Haut-Lévêque ( ANATOMOPATHOLOGIE ), Clinical Neurology Oxford ( CLINICAL NEUROLOGY ), Université Montpellier 1 ( UM1 ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de synthèse organique ( DCSO ), Centre National de la Recherche Scientifique ( CNRS ) -École polytechnique ( X ), FLAveur, VIsion et Comportement du consommateur ( FLAVIC ), Etablissement National d'Enseignement Supérieur Agronomique de Dijon ( ENESAD ) -Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre de Biologie Intégrative (CBI), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB), École polytechnique (X)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Recherche Agronomique (INRA)-Etablissement National d'Enseignement Supérieur Agronomique de Dijon (ENESAD)-Université de Bourgogne (UB)
Subjects: MESH: Sequence Analysis, DNA, MESH : Molecular Sequence Data, MESH : Transcription Factors, MESH : DNA, Complementary, Chick Embryo, MESH: Base Sequence, MESH : Extremities, Mice, 0302 clinical medicine, Complementary, MESH : Chick Embryo, MESH: Gene Expression Regulation, Developmental, Developmental, MESH: Animals, In Situ Hybridization, Regulation of gene expression, Genetics, 0303 health sciences, Gene Expression Regulation, Developmental, MESH : In Situ Hybridization, MESH: Transcription Factors, MESH: Chick Embryo, Cell biology, MESH : Connective Tissue, medicine.anatomical_structure, Connective Tissue, Sequence Analysis, DNA, Complementary, animal structures, MESH: Connective Tissue, Mesenchyme, Molecular Sequence Data, In situ hybridization, Biology, 03 medical and health sciences, Limb bud, MESH: In Situ Hybridization, MESH : Mice, medicine, Animals, Limb development, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Biology, Gene, Transcription factor, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Mice, 030304 developmental biology, MESH: Molecular Sequence Data, Base Sequence, Extremities, Sequence Analysis, DNA, DNA, MESH: DNA, Complementary, Gene Expression Regulation, MESH : Base Sequence, MESH : Animals, MESH : Gene Expression Regulation, Developmental, MESH: Extremities, Transcription Factor Gene, 030217 neurology & neurosurgery, Transcription Factors, Developmental Biology, MESH : Sequence Analysis, DNA
Abstract: The COE (Collier/Olf/EBF) family of transcription factors comprises a single member in Drosophila and four members in human and mice. We have examined by in situ hybridization the expression patterns of each ebf/coe gene during limb development in mouse and chicken embryos. Expression of mouse ebf1, 2 and 3 is detected in mesenchymal cells from stages E10.5-11, expression of ebf2 being restricted to the presumptive zeugopod. Cross sections of mouse and chicken limb buds at several stages reveal that ebfs are specifically expressed in the connective tissues surrounding chondrogenic condensations and forming tendons. They thus represent useful new markers for studying vertebrate limb development, particularly formation of ligaments.
Published: 2004
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34. The HBZ factor of human T-cell leukemia virus type I dimerizes with transcription factors JunB and c-Jun and modulates their transcriptional activity

Author: Marc Piechaczyk, Jean-Michel Mesnard, Charlotte Arpin, Gilles Gaudray, Christian Devaux, Jihane Basbous, Infections rétrovirales et signalisation cellulaire ( IRSC ), Université Montpellier 1 ( UM1 ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Génétique Moléculaire de Montpellier ( IGMM ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), ARC, Infections rétrovirales et signalisation cellulaire (IRSC), Université Montpellier 1 (UM1)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique Moléculaire de Montpellier (IGMM), and Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)
Subjects: Transcription, Genetic, MESH : Hela Cells, Proto-Oncogene Proteins c-jun, Retroviridae Proteins, MESH: Streptavidin, MESH : Blotting, Western, Biochemistry, MESH: Down-Regulation, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH: Protein Structure, Tertiary, 0302 clinical medicine, Transcription (biology), Genes, Reporter, MESH: Gene Products, tax, MESH : Trans-Activation (Genetics), MESH: Animals, MESH : Viral Proteins, 0303 health sciences, c-jun, MESH : Protein Binding, MESH: Transcription Factors, MESH : beta-Galactosidase, MESH : Precipitin Tests, MESH : Human T-lymphotropic virus 1, MESH: Transcription Factor AP-1, MESH: Leucine Zippers, 3. Good health, MESH: COS Cells, MESH: Promoter Regions (Genetics), Basic-Leucine Zipper Transcription Factors, MESH : Transcription Factor AP-1, 030220 oncology & carcinogenesis, COS Cells, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, JunB, MESH : Protein Structure, Tertiary, MESH : Proto-Oncogene Proteins c-jun, Transcriptional Activation, MESH : Glutathione Transferase, Blotting, Western, Biotin, Down-Regulation, MESH: Basic-Leucine Zipper Transcription Factors, Transfection, [ SDV.MP.VIR ] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 03 medical and health sciences, Viral Proteins, MESH : Basic-Leucine Zipper Transcription Factors, Humans, MESH: Protein Binding, MESH: Blotting, Western, Collagenases, E2F, Molecular Biology, MESH: Glutathione Transferase, MESH: Human T-lymphotropic virus 1, MESH: Humans, MESH: Proto-Oncogene Proteins c-jun, MESH: Genes, Reporter, MESH : Humans, Precipitin Tests, MESH : Promoter Regions (Genetics), Protein Structure, Tertiary, MESH : Streptavidin, Microscopy, Fluorescence, MESH: Binding Sites, HTLV-1, MESH: Luciferases, HeLa Cells, Transcription Factors, Time Factors, MESH : Transcription Factors, MESH : Microscopy, Fluorescence, MESH : DNA, Complementary, MESH: Collagenases, MESH: Microscopy, Fluorescence, MESH : Biotin, MESH : Down-Regulation, Transactivation, hemic and lymphatic diseases, MESH : RNA, MESH: Precipitin Tests, Luciferases, Promoter Regions, Genetic, Glutathione Transferase, Human T-lymphotropic virus 1, MESH : Collagenases, Gene Products, tax, MESH : Genes, Reporter, MESH: beta-Galactosidase, MESH : Dimerization, MESH: Genome, Viral, MESH : Transfection, MESH : COS Cells, Dimerization, MESH : Genome, Viral, Protein Binding, MESH : Time Factors, Leucine zipper, DNA, Complementary, JUNB, [SDV.CAN]Life Sciences [q-bio]/Cancer, Genome, Viral, Biology, MESH: Two-Hybrid System Techniques, MESH: RNA, Two-Hybrid System Techniques, MESH: Biotin, Animals, Transcription factor, 030304 developmental biology, MESH : Luciferases, Leucine Zippers, Binding Sites, Activator (genetics), MESH : Gene Products, tax, MESH: Transcription, Genetic, MESH: Transfection, MESH: Time Factors, c-Jun, MESH : Transcription, Genetic, Cell Biology, MESH: DNA, Complementary, beta-Galactosidase, AP-1, Molecular biology, MESH: Viral Proteins, Transcription Factor AP-1, MESH: Hela Cells, MESH: Dimerization, MESH : Two-Hybrid System Techniques, MESH: Trans-Activation (Genetics), RNA, MESH : Leucine Zippers, Streptavidin, MESH : Animals, MESH : Binding Sites
Abstract: The human T-cell leukemia virus type I (HTLV-I)-encoded Tax protein activates transcription from the viral promoter via association with the cellular basic leucine zipper factor cAMP-response element-binding protein-2. Tax is also able to induce cellular transformation of T lymphocytes probably by modulating transcriptional activity of cellular factors, including nuclear factor-kappaB, E2F, activator protein-1 (AP-1), and p53. Recently, we characterized in HTLV-I-infected cells the presence of a novel viral protein, HBZ, encoded by the complementary strand of the HTLV-I RNA genome (Gaudray, G., Gachon, F., Basbous, J., Biard-Piechaczyk, M., Devaux, C., and Mesnard, J.-M. (2002) J. Virol. 76, 12813-12822). HBZ is a nuclear basic leucine zipper protein that down-regulates Tax-dependent viral transcription by inhibiting the binding of cAMP-response element-binding protein-2 to the HTLV-I promoter. In searching for other cellular targets of HBZ, we identified two members of the Jun family, JunB and c-Jun. Co-immunoprecipitation and cellular colocalization confirmed that HBZ interacts in vivo with JunB and c-Jun. When transiently introduced into CEM cells with a reporter gene containing the AP-1 site from the collagenase promoter, HBZ suppressed transactivation by c-Jun. On the other hand, the combination of HBZ with Jun-B had higher transcriptional activity than JunB alone. Consistent with the structure of its basic domain, we demonstrate that HBZ decreases the DNA-binding activity of c-Jun and JunB. Last, we show that c-Jun is no longer capable of activating the basal expression of the HTLV-I promoter in the presence of HBZ in vivo. Our results support the hypothesis that HBZ could be a negative modulator of the Tax effect by controlling Tax expression at the transcriptional level and by attenuating activation of AP-1 by Tax.
Published: 2003
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35. Genome-wide search for type 2 diabetes in Japanese affected sib-pairs confirms susceptibility genes on 3q, 15q, and 20q and identifies two new candidate Loci on 7p and 11p

Author: Philippe Froguel, Kazuo Hara, Kazuki Yasuda, Shuichi Otabe, Cécile Lecoeur, Takashi Kadowaki, Kazuyuki Tobe, Céline Populaire, Philippe Boutin, Emmanuelle Durand, Terumasa Okada, Christian Dina, Yasumichi Mori, Vincent Vatin, Génétique des maladies multifactorielles (GMM), Université de Lille, Droit et Santé - Centre National de la Recherche Scientifique (CNRS), Science et Ingénierie des Matériaux et Procédés (SIMaP), Université Joseph Fourier - Grenoble 1 (UJF) - Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP) - Institut National Polytechnique de Grenoble (INPG) - Centre National de la Recherche Scientifique (CNRS) - Université Grenoble Alpes (UGA), Physique, Aucune, Institut de Chimie de la Matière Condensée de Bordeaux (ICMCB), Université de Bordeaux (UB) - Centre National de la Recherche Scientifique (CNRS), Développement artériel, Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM), Mercator Océan, Société Civile CNRS Ifremer IRD Météo-France SHOM, Itoh laboratory, Division of Materials Physics, Osaka University [Osaka] - School of Engineering Science, Section of Genomic Medicine, Imperial College London, Genome Centre, Imperial College London - Hammersmith campus, Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National Polytechnique de Grenoble (INPG)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Polytechnique de Bordeaux-Université de Bordeaux (UB), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Osaka University [Osaka]-School of Engineering Science, Imperial College London-Hammersmith campus, Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), and Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)
Subjects: MESH : Chromosomes, Human, Pair 20, MESH : Transcription Factors, Genetic Linkage, MESH: Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Endocrinology, Diabetes and Metabolism, Chromosomes, Human, Pair 20, MESH : Japan, Type 2 diabetes, MESH: Genetic Markers, MESH : Chromosomes, Human, Pair 3, Genome, MESH : Chromosomes, Human, Pair 1, MESH : Chromosomes, Human, Pair 7, 0302 clinical medicine, Japan, MESH : Diabetes Mellitus, Type 2, MESH: Chromosomes, Human, Pair 20, MESH : Genetic Markers, Age of Onset, MESH: Japan, Genetics, 0303 health sciences, education.field_of_study, MESH: Middle Aged, MESH: Nuclear Family, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, MESH: Genetic Predisposition to Disease, Chromosome Mapping, MESH: Transcription Factors, Middle Aged, MESH : Adult, MESH : Chromosomes, Human, Pair 15, 3. Good health, MESH : Age of Onset, DNA-Binding Proteins, Hepatocyte Nuclear Factor 4, Chromosomes, Human, Pair 1, Chromosomes, Human, Pair 3, MESH: Hepatocyte Nuclear Factor 4, MESH : DNA-Binding Proteins, MESH : Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Chromosomes, Human, Pair 7, MESH: Diabetes Mellitus, Type 2, Adult, Genetic Markers, MESH : Genome, Human, MESH: Chromosomes, Human, Pair 7, MESH: Chromosomes, Human, Pair 1, MESH: Age of Onset, Population, MESH: Chromosomes, Human, Pair 3, 030209 endocrinology & metabolism, Susceptibility gene, Biology, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, MESH: Phosphoproteins, Nuclear Family, 03 medical and health sciences, MESH : Hepatocyte Nuclear Factor 4, Internal Medicine, medicine, Humans, Genetic Predisposition to Disease, MESH : Middle Aged, education, Gene, MESH: Genome, Human, 030304 developmental biology, Linkage (software), Chromosomes, Human, Pair 15, MESH: Humans, Genome, Human, MESH : Humans, Chromosome, MESH: Adult, medicine.disease, Phosphoproteins, Sib pairs, Diabetes Mellitus, Type 2, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, MESH : Genetic Predisposition to Disease, MESH : Nuclear Family, MESH : Phosphoproteins, MESH: Chromosome Mapping, MESH: Linkage (Genetics), MESH: DNA-Binding Proteins, MESH : Linkage (Genetics), MESH : Chromosome Mapping, Transcription Factors, MESH: Chromosomes, Human, Pair 15
Abstract: The genetic background that predisposes the Japanese population to type 2 diabetes is largely unknown. Therefore, we conducted a 10-cM genome-wide scan for type 2 diabetes traits in the 359 affected individuals from 159 families, yielding 224 affected sib-pairs of Japanese origin. Nonparametric multipoint linkage analyses performed in the whole population showed one suggestive linked region on 11p13-p12 (maximum logarithm of odds score [MLS] 3.08, near Pax6) and seven potentially linked regions (MLS >1.17) at 1p36-p32, 2q34, 3q26-q28, 6p23, 7p22-p21, 15q13-q21, and 20q12-q13 (near the gene for hepatocyte nuclear factor-4α [HNF-4α]). Subset analyses according to maximal BMI and early age at diagnosis added suggestive evidence of linkage with type 2 diabetes at 7p22-p21 (MLS 3.51), 15q13-q21 (MLS 3.91), and 20q12-q13 (MLS 2.32). These results support previous indication for linkage found on chromosome 3q, 15q, and 20q in other populations and identifies two new potential loci on 7p and 11p that may confer genetic risk for type 2 diabetes in the Japanese population.
Published: 2002

36. Adenovirus-mediated overexpression of sterol regulatory element binding protein-1c mimics insulin effects on hepatic gene expression and glucose homeostasis in diabetic mice

Author: Isabelle Hainault, Dalila Azzout-Marniche, Pascal Ferré, Lydia Bertry-Coussot, Dominique Bécard, Fabienne Foufelle, Physiologie de la Nutrition et du Comportement Alimentaire ( PNCA ), Institut National de la Recherche Agronomique ( INRA ) -AgroParisTech, Centre de Recherche des Cordeliers ( CRC ), Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Physiologie de la Nutrition et du Comportement Alimentaire (PNCA), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Azzout-Marniche, Dalila, AgroParisTech-Institut National de la Recherche Agronomique (INRA), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE)
Subjects: Male, MESH : RNA, Messenger, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], MESH: CCAAT-Enhancer-Binding Proteins, MESH: Recombinant Proteins, Mice, 0302 clinical medicine, Homeostasis, Insulin, Glucose homeostasis, MESH: Animals, 0303 health sciences, MESH: Mice, Inbred CBA, Glycogen, Gene Transfer Techniques, MESH: Adenoviridae, [SDV.BBM.MN]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], MESH: Transcription Factors, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [ SDV.MHEP.EM ] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, MESH : Genetic Vectors, 3. Good health, MESH : DNA-Binding Proteins, MESH : Diabetes Mellitus, Experimental, Sterol Regulatory Element Binding Protein 1, medicine.medical_specialty, MESH: Gene Expression, MESH: Gene Transfer Techniques, MESH: Insulin, [ SDV.BBM.BM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Adenoviridae, MESH: Sterol Regulatory Element Binding Protein 1, 03 medical and health sciences, MESH : Sterol Regulatory Element Binding Protein 1, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], RNA, Messenger, MESH : Gene Transfer Techniques, MESH : Injections, Intraperitoneal, MESH : Glucose, Glucokinase, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, medicine.disease, MESH : Gene Expression, Glucose, Endocrinology, [SDV.BBM.MN] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], chemistry, CCAAT-Enhancer-Binding Proteins, Mice, Inbred CBA, MESH: Liver, Transcription Factors, MESH : Transcription Factors, MESH : Insulin, MESH : Mice, Inbred CBA, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, Gene Expression, [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, chemistry.chemical_compound, MESH: Genetic Vectors, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], MESH: Diabetes Mellitus, Experimental, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [ SDV.MHEP.PHY ] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Recombinant Proteins, MESH: Glucose, DNA-Binding Proteins, Liver, MESH : CCAAT-Enhancer-Binding Proteins, MESH: Homeostasis, MESH : Homeostasis, Phosphoenolpyruvate carboxykinase, MESH: Injections, Intraperitoneal, Injections, Intraperitoneal, MESH : Recombinant Proteins, MESH : Male, Genetic Vectors, 030209 endocrinology & metabolism, Biology, Diabetes Mellitus, Experimental, [ SDV.BC.IC ] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [ SDV.BBM.MN ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], Diabetes mellitus, Internal medicine, MESH : Mice, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Internal Medicine, medicine, Animals, MESH : Adenoviridae, MESH: Mice, Transcription factor, MESH: RNA, Messenger, 030304 developmental biology, [ SDV.BC.BC ] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], MESH : Liver, Metabolism, MESH: Male, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, MESH : Animals, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, MESH: DNA-Binding Proteins
Abstract: International audience; In vitro, the transcription factor sterol regulatory element binding protein-1c (SREBP-1c) mimics the positive effects of insulin on hepatic genes involved in glucose utilization, such as glucokinase (GK) and enzymes of the lipogenic pathway, suggesting that it is a key factor in the control of hepatic glucose metabolism. Decreased glucose utilization and increased glucose production by the liver play an important role in the development of the hyperglycemia in diabetic states. We thus reasoned that if SREBP-1c is indeed a mediator of hepatic insulin action, a hepatic targeted overexpression of SREBP-1c should greatly improve glucose homeostasis in diabetic mice. This was achieved by injecting streptozotocin-induced diabetic mice with a recombinant adenovirus containing the cDNA of the mature, transcriptionally active form of SREBP-1c. We show here that overexpressing SREBP-1c specifically in the liver of diabetic mice induces GK and lipogenic enzyme gene expression and represses the expression of phosphoenolpyruvate carboxykinase, a key enzyme of the gluconeogenic pathway. This in turn increases glycogen and triglyceride hepatic content and leads to a marked decrease in hyperglycemia in diabetic mice. We conclude that SREBP-1c has a major role in vivo in the long-term control of glucose homeostasis by insulin.
Published: 2001

37. The BTB/POZ domain of the regulatory proteins Bric à brac 1 (BAB1) and Bric à brac 2 (BAB2) interacts with the novel Drosophila TAF(II) factor BIP2/dTAF(II)155

Author: Jan Larsson, Jean-Christophe Pointud, Bernard Dastugue, Jean-Louis Couderc, Interactions génétiques et cellulaires au cours de la différenciation, Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of microbiology, Umeå University, Université d'Auvergne - Clermont-Ferrand I ( UdA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Couderc, Jean-Louis
Subjects: MESH : Molecular Sequence Data, Time Factors, MESH : Transcription Factors, Transcription, Genetic, MESH: Drosophila, MESH : Models, Genetic, Plasma protein binding, MESH : Blotting, Western, MESH: Protein Structure, Tertiary, Protein structure, Transcription (biology), Transcriptional regulation, Drosophila Proteins, MESH: Animals, transcriptional regulation, MESH: Models, Genetic, BTB/POZ domain, TAFII, [SDV.BDD]Life Sciences [q-bio]/Development Biology, Genetics, MESH : Blotting, Northern, MESH : Protein Binding, MESH: Transcription Factors, DNA-Binding Proteins, MESH: Repressor Proteins, Drosophila, MESH : DNA-Binding Proteins, MESH : Repressor Proteins, MESH : Protein Structure, Tertiary, Drosophila Protein, MESH : Time Factors, Plasmids, Protein Binding, MESH: Drosophila Proteins, Blotting, Western, Molecular Sequence Data, Biology, MESH: Two-Hybrid System Techniques, Chromatin remodeling, MESH: Plasmids, Two-Hybrid System Techniques, [SDV.BDD] Life Sciences [q-bio]/Development Biology, MESH: Blotting, Northern, MESH: Blotting, Western, MESH: Protein Binding, Animals, [ SDV.BDD ] Life Sciences [q-bio]/Development Biology, MESH : Drosophila, Transcription factor, Molecular Biology, MESH: Molecular Sequence Data, Models, Genetic, MESH: Transcription, Genetic, MESH: Time Factors, MESH : Transcription, Genetic, Cell Biology, MESH : Drosophila Proteins, Blotting, Northern, Protein Structure, Tertiary, Repressor Proteins, MESH : Two-Hybrid System Techniques, MESH : Plasmids, MESH : Animals, MESH: DNA-Binding Proteins, Developmental Biology, Transcription Factors
Abstract: International audience; The BTB/POZ domain is an evolutionarily conserved protein-protein interaction domain present in the N-terminal region of numerous transcription factors involved in development, chromatin remodeling, and human cancers. This domain is involved in homomeric and heteromeric associations with other BTB/POZ domains. The Drosophila BTB/POZ proteins Bric ?rac 1 (BAB1) and Bric ?rac 2 (BAB2) are developmentally regulated transcription factors which are involved in pattern formation along the proximo-distal axis of the leg and antenna, in the morphogenesis of the adult ovaries, and in the control of sexually dimorphic characters. We have identified partners of the BAB1 protein by using the two-hybrid system. The characterization of one of these proteins, called BIP2 for BAB Interacting Protein 2, is presented. BIP2 is a novel Drosophila TATA-box Protein Associated Factor (TAF(II)), also named dTAF(II)155. We show that the BTB/POZ domains of BAB1 and BAB2 are sufficient to mediate a direct interaction with BIP2/dTAF(II)155. This provides a direct link between these BTB/POZ transcription factors and the basal transcriptional machinery. We discuss the implications of the interaction between a BTB/POZ domain and a TAF(II) for the molecular mechanisms of transcriptional control mediated by BTB/POZ transcription factors.
Published: 2001
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38. beta-cell genes and diabetes: quantitative and qualitative differences in the pathophysiology of hepatic nuclear factor-1alpha and glucokinase mutations

Author: Phillipe Froguel, Andrew T. Hattersley, P. M. Clark, Ewan R. Pearson, Michael P. Bulman, Amanda Stride, Maggie Shepherd, Gilberto Velho, Sian Ellard, Timothy M. Frayling, Immunologie, génétique et traitement des maladies métaboliques et du diabète ( UMR_S 561 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Génétique des maladies multifactorielles ( GMM ), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique ( CNRS ), Section of Genomic Medicine, Imperial College London, Genome Centre, Imperial College London-Hammersmith campus, Immunologie, génétique et traitement des maladies métaboliques et du diabète (UMR_S 561), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Génétique des maladies multifactorielles (GMM), and Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS)
Subjects: Blood Glucose, Male, MESH : Transcription Factors, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, MESH : Insulin, MESH : Fasting, MESH : Diabetes Mellitus, Type 2, Glucokinase, Insulin, Glycolysis, MESH : Female, Hepatocyte Nuclear Factor 1-alpha, [ SDV.GEN.GH ] Life Sciences [q-bio]/Genetics/Human genetics, MESH : Proinsulin, Glucose tolerance test, medicine.diagnostic_test, MESH : Glucokinase, MESH: Hepatocyte Nuclear Factor 1, Age Factors, Nuclear Proteins, MESH: Transcription Factors, MESH: Glucokinase, Fasting, MESH : Adult, MESH: Genes, DNA-Binding Proteins, Hepatocyte nuclear factors, MESH: Insulin Resistance, MESH: Proinsulin, Hepatocyte Nuclear Factor 1, MESH : Genes, MESH : Hepatocyte Nuclear Factor 1-alpha, Female, MESH : DNA-Binding Proteins, Beta cell, MESH : Mutation, MESH : Insulin Resistance, MESH : Hepatocyte Nuclear Factor 1-beta, MESH: Diabetes Mellitus, Type 2, Proinsulin, Adult, medicine.medical_specialty, MESH: Mutation, MESH: Glucose Tolerance Test, MESH : Male, MESH: Fasting, MESH: Insulin, Biology, MESH : Family Health, MESH : Glucose Tolerance Test, MESH : Hepatocyte Nuclear Factor 1, Islets of Langerhans, Insulin resistance, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Humans, MESH : Islets of Langerhans, MESH: Hepatocyte Nuclear Factor 1-beta, MESH: Hepatocyte Nuclear Factor 1-alpha, Hepatocyte Nuclear Factor 1-beta, MESH: Age Factors, Family Health, MESH: Humans, MESH: Islets of Langerhans, MESH : Humans, MESH : Nuclear Proteins, MESH: Adult, Glucose Tolerance Test, medicine.disease, MESH : Blood Glucose, MESH: Male, Endocrinology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Diabetes Mellitus, Type 2, Genes, Mutation, MESH: Blood Glucose, MESH: Family Health, MESH : Age Factors, Insulin Resistance, MESH: Nuclear Proteins, MESH: Female, MESH: DNA-Binding Proteins, Transcription Factors
Abstract: Mutations in the beta-cell genes encoding the glycolytic enzyme glucokinase (GCK) and the transcription factor hepatocyte nuclear factor (HNF)-1alpha are the most common causes of maturity-onset diabetes of the young (MODY). Studying patients with mutations in these genes gives insights into the functions of these two critical beta-cell genes in humans. We studied 178 U.K. and French MODY family members, including 45 GCK mutation carriers and 40 HNF-1alpha mutation carriers. Homeostasis model assessment of fasting insulin and glucose showed reduced beta-cell function in both GCK (48% controls, P
Published: 2001

39. Characterization of the Role of AMP-Activated Protein Kinase in the Regulation of Glucose-Activated Gene Expression Using Constitutively Active and Dominant Negative Forms of the Kinase

Author: Woods, Angela, Azzout-Marniche, Dalila, Foretz, Marc, Stein, Silvie, Lemarchand, Patricia, Ferré, P., Foufelle, Fabienne, Carling, David, Ferré, Pascal, Hammersmith Hospital, Charing Cross Hospital & Imperial College, Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Cellular Stress Group, Imperial College London-Hammersmith Hospital-Medical Research Council Clinical Sciences Centre, Physiologie de la Nutrition et du Comportement Alimentaire ( PNCA ), Institut National de la Recherche Agronomique ( INRA ) -AgroParisTech, [Institut Cochin] Département Endocrinologie, métabolisme, diabète (EMD) ( EMD ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de Recherche des Cordeliers ( CRC ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -École pratique des hautes études ( EPHE ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Physiologie de la Nutrition et du Comportement Alimentaire (PNCA), AgroParisTech-Institut National de la Recherche Agronomique (INRA), [Institut Cochin] Département Endocrinologie, métabolisme, diabète (EMD) (EMD), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), FORETZ, Marc, and Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE)
Subjects: MESH : Cell Line, MESH : Molecular Sequence Data, MESH : Transcription Factors, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, Gene Expression, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], MESH: Amino Acid Sequence, AMP-Activated Protein Kinases, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, MESH: Multienzyme Complexes, MESH : Proteins, 0302 clinical medicine, AMP-activated protein kinase, Gene expression, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], MESH : Female, MESH: Animals, MESH: Proteins, MESH: AMP-Activated Protein Kinases, [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Regulation of gene expression, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 0303 health sciences, biology, Kinase, MESH : Rats, [ SDV.MHEP.PHY ] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], MESH : Amino Acid Sequence, MESH: Gene Expression Regulation, Enzymologic, MESH : AMP-Activated Protein Kinases, Nuclear Proteins, [SDV.BBM.MN]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], MESH: Transcription Factors, MESH : Multienzyme Complexes, [ SDV.MHEP.EM ] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, MESH: Glucose, Biochemistry, Liver, MESH: Pyruvate Kinase, Female, MESH: Fatty Acid Synthases, MESH : Protein-Serine-Threonine Kinases, MESH: Rats, Molecular Sequence Data, Pyruvate Kinase, [ SDV.BBM.BM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Protein Serine-Threonine Kinases, MESH : Rats, Wistar, Gene Expression Regulation, Enzymologic, MESH: Protein-Serine-Threonine Kinases, MESH : Gene Expression Regulation, Enzymologic, [ SDV.BC.IC ] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Cell Line, 03 medical and health sciences, [ SDV.BBM.MN ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], Multienzyme Complexes, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, Humans, Amino Acid Sequence, Rats, Wistar, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Protein kinase A, Molecular Biology, Transcription factor, 030304 developmental biology, MESH: Humans, MESH: Molecular Sequence Data, MESH : Glucose, MESH : Humans, [ SDV.BC.BC ] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], AMPK, MESH : Acetyl-CoA Carboxylase, MESH : Liver, MESH : Nuclear Proteins, Proteins, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Cell Biology, MESH: Rats, Wistar, MESH : Pyruvate Kinase, Rats, MESH: Cell Line, Glucose, biology.protein, MESH : Animals, MESH: Acetyl-CoA Carboxylase, MESH : Fatty Acid Synthases, Fatty Acid Synthases, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, MESH: Female, MESH: Nuclear Proteins, 030217 neurology & neurosurgery, Pyruvate kinase, Acetyl-CoA Carboxylase, Transcription Factors, MESH: Liver
Abstract: International audience; In the liver, glucose induces the expression of a number of genes involved in glucose and lipid metabolism, e.g., those encoding L-type pyruvate kinase and fatty acid synthase. Recent evidence has indicated a role for the AMP-activated protein kinase (AMPK) in the inhibition of glucose-activated gene expression in hepatocytes. It remains unclear, however, whether AMPK is involved in the glucose induction of these genes. In order to study further the role of AMPK in regulating gene expression, we have generated two mutant forms of AMPK. One of these (alpha1(312)) acts as a constitutively active kinase, while the other (alpha1DN) acts as a dominant negative inhibitor of endogenous AMPK. We have used adenovirus-mediated gene transfer to express these mutants in primary rat hepatocytes in culture in order to determine their effect on AMPK activity and the transcription of glucose-activated genes. Expression of alpha1(312) increased AMPK activity in hepatocytes and blocked completely the induction of a number of glucose-activated genes in response to 25 mM glucose. This effect is similar to that observed following activation of AMPK by 5-amino-imidazolecarboxamide riboside. Expression of alpha1DN markedly inhibited both basal and stimulated activity of endogenous AMPK but had no effect on the transcription of glucose-activated genes. Our results suggest that AMPK is involved in the inhibition of glucose-activated gene expression but not in the induction pathway. This study demonstrates that the two mutants we have described will provide valuable tools for studying the wider physiological role of AMPK.
Published: 2000
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40. Insulin effects on sterol regulatory-element-binding protein-1c (SREBP-1c) transcriptional activity in rat hepatocytes

Author: Dalila Azzout-Marniche, Marc Foretz, Fabienne Foufelle, Pascal Ferré, Colette Guichard, Dominique Bécard, Physiologie de la Nutrition et du Comportement Alimentaire (PNCA), AgroParisTech-Institut National de la Recherche Agronomique (INRA), [Institut Cochin] Département Endocrinologie, métabolisme, diabète (EMD) (EMD), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiologie de la Nutrition et du Comportement Alimentaire ( PNCA ), Institut National de la Recherche Agronomique ( INRA ) -AgroParisTech, [Institut Cochin] Département Endocrinologie, métabolisme, diabète (EMD) ( EMD ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de Recherche des Cordeliers ( CRC ), Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE)
Subjects: MESH: Protein Precursors, Transcription, Genetic, medicine.medical_treatment, MESH : Hepatocytes, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Biochemistry, MESH: CCAAT-Enhancer-Binding Proteins, MESH: Hepatocytes, 0302 clinical medicine, Insulin receptor substrate, Insulin, MESH: Animals, Enzyme Inhibitors, MESH : Immunoblotting, Cells, Cultured, Protein Synthesis Inhibitors, 0303 health sciences, MESH : Cell Nucleus, MESH : Glucokinase, MESH: Immunoblotting, food and beverages, [SDV.BBM.MN]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], MESH: Glucokinase, MESH: Transcription Factors, [ SDV.MHEP.EM ] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 3. Good health, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], 030220 oncology & carcinogenesis, MESH : DNA-Binding Proteins, Sterol Regulatory Element Binding Protein 1, MESH: Cells, Cultured, MESH: Cell Nucleus, MESH: Enzyme Activation, MESH : Cell Membrane, [ SDV.BBM.BM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, MESH: Insulin, digestive system, 03 medical and health sciences, MESH: Sterol Regulatory Element Binding Protein 1, MESH : Sterol Regulatory Element Binding Protein 1, MESH: Blotting, Northern, Protein Precursors, Molecular Biology, Dose-Response Relationship, Drug, Glucokinase, Endoplasmic reticulum, Cell Membrane, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Sterol regulatory element-binding protein, Enzyme Activation, MESH: Phosphatidylinositol 3-Kinases, CCAAT-Enhancer-Binding Proteins, MESH: Female, Transcription Factors, MESH: Signal Transduction, Time Factors, MESH : Transcription Factors, MESH : Insulin, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, MESH : Dose-Response Relationship, Drug, Endoplasmic Reticulum, MESH: Dose-Response Relationship, Drug, Phosphatidylinositol 3-Kinases, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], polycyclic compounds, MESH : Female, Cycloheximide, MESH: Cycloheximide, MESH : Protein Precursors, MESH : Endoplasmic Reticulum, MESH : Rats, [ SDV.MHEP.PHY ] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], MESH : Blotting, Northern, DNA-Binding Proteins, Fatty acid synthase, MESH : CCAAT-Enhancer-Binding Proteins, MESH: Enzyme Inhibitors, Female, lipids (amino acids, peptides, and proteins), MESH : Time Factors, Research Article, Signal Transduction, MESH: Rats, Immunoblotting, Biology, [ SDV.BC.IC ] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [ SDV.BBM.MN ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], MESH: Endoplasmic Reticulum, MESH : Cycloheximide, MESH : Cells, Cultured, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, MESH : Protein Synthesis Inhibitors, Transcription factor, 030304 developmental biology, MESH : Signal Transduction, Cell Nucleus, MESH : Enzyme Inhibitors, MESH: Protein Synthesis Inhibitors, MESH: Transcription, Genetic, MESH: Time Factors, [ SDV.BC.BC ] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], MESH : Transcription, Genetic, MESH : Phosphatidylinositol 3-Kinases, Cell Biology, Blotting, Northern, Rats, biology.protein, Hepatocytes, MESH : Animals, MESH : Enzyme Activation, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, MESH: DNA-Binding Proteins, MESH: Cell Membrane
Abstract: International audience; The transcription factor sterol regulatory-element-binding protein-1c (SREBP-1c) plays a major role in the effect of insulin on the transcription of hepatic genes such as glucokinase and fatty acid synthase. We show here in cultured rat hepatocytes that insulin, through activation of the phosphatidylinositol 3-kinase pathway increases the abundance of the precursor form of SREBP-1c in endoplasmic reticulum. This precursor form is then rapidly cleaved, possibly irrespective of the continuous presence of insulin, leading to an increased content of the nuclear mature form of SREBP-1c. Nevertheless, the increased amount of the mature form of SREBP-1c in the nucleus is not a prerequisite for the rapid effect of insulin on the transcription of genes such as glucokinase, suggesting that additional actions of the hormone are involved, such as the activation of the nuclear form of SREBP-1c or of an unidentified SREBP-1c partner.
Published: 2000

41. Genetic identification of neurons controlling a sexually dimorphic behaviour

Author: Gatti , S., Ferveur , J. F., Martin , J. R., Neurobiologie de l'apprentissage, de la mémoire et de la communication ( NAMC ), Université Paris-Sud - Paris 11 ( UP11 ) -Centre National de la Recherche Scientifique ( CNRS ), Développement et Communication Chimique chez les Insectes ( DCCI ), and Centre National de la Recherche Scientifique ( CNRS ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement
Subjects: MESH : Recombinant Fusion Proteins, MESH : Transcription Factors, MESH : Male, fungi, MESH : Animals, Genetically Modified, MESH : Sex Characteristics, MESH : Nuclear Proteins, MESH : Neurons, MESH : Nervous System Physiology, MESH : Saccharomyces cerevisiae Proteins, MESH : Locomotion, [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH : Drosophila melanogaster, MESH : Fungal Proteins, MESH : Female, MESH : Animals, MESH : Sexual Behavior, Animal, MESH : Motor Activity
Abstract: In the fruit fly Drosophila melanogaster, locomotor activity is sexually dimorphic: female flies constantly modulate their activity pattern whereas males show a steadier, stereotyped walking pace [1]. Here, we mapped the area of the brain controlling this behavioural dimorphism. Adult male Drosophila expressing a dominant feminising transgene in a small cluster of neurons in the pars intercerebralis exhibited a female-like pattern of locomotor activity. Genetic ablation of these neurons prevented the feminisation of the locomotor activity of transgenic males. The results suggest that this cluster of neurons modulates sex-specific activity, but is not involved in initiating fly locomotion. Nor does it control male courtship behaviour, because feminisation of courtship was not correlated with the feminisation of locomotor activity.
Published: 2000
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42. Glutamate Induces Phosphorylation of Elk-1 and CREB, Along with c -fos Activation, via an Extracellular Signal-Regulated Kinase-Dependent Pathway in Brain Slices

Author: Marie-Jo Besson, Peter Vanhoutte, Jean-Vianney Barnier, Jocelyne Caboche, Robert A. Hipskind, Christiane Pagès, Bernard Guibert, Neurobiologie des processus adaptatifs (NPA), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Institut Alfred Fessard, Centre National de la Recherche Scientifique (CNRS), Institut des Neurosciences (IDN), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut des Neurosciences, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ), Centre National de la Recherche Scientifique ( CNRS ), Institut de Neurobiologie Alfred Fessard ( INAF ), Institut de Génétique Moléculaire de Montpellier ( IGMM ), and Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: MAPK/ERK pathway, Male, MESH : Proto-Oncogene Proteins c-raf, MESH : Transcription Factors, Mitogen-Activated Protein Kinase 3, MESH : Corpus Striatum, MAP Kinase Kinase 1, MESH : MAP Kinase Kinase 1, Mitogen-activated protein kinase kinase, MESH : Ca(2+)-Calmodulin Dependent Protein Kinase, Rats, Sprague-Dawley, MESH : Phosphorylation, 0302 clinical medicine, MESH : Glutamic Acid, MESH : Trans-Activation (Genetics), Phosphorylation, Cyclic AMP Response Element-Binding Protein, Cell Growth and Development, MESH : Mitogen-Activated Protein Kinase Kinases, Mitogen-Activated Protein Kinase 1, 0303 health sciences, MESH : Mitogen-Activated Protein Kinase 1, biology, MESH : Mitogen-Activated Protein Kinase 3, MESH : Gene Expression Regulation, Kinase, MESH : Rats, MESH : Cyclic AMP Response Element-Binding Protein, Brain, Protein-Tyrosine Kinases, DNA-Binding Proteins, MESH : Proto-Oncogene Proteins, Proto-Oncogene Proteins c-raf, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH : DNA-Binding Proteins, Signal transduction, MESH : Kinetics, Mitogen-Activated Protein Kinases, Proto-Oncogene Proteins c-fos, Signal Transduction, MESH : Protein-Serine-Threonine Kinases, Transcriptional Activation, MESH : Male, Glutamic Acid, Protein Serine-Threonine Kinases, CREB, MESH : Extracellular Space, 03 medical and health sciences, Proto-Oncogene Proteins, MESH : Protein-Tyrosine Kinases, Animals, Protein kinase A, Molecular Biology, 030304 developmental biology, ets-Domain Protein Elk-1, MESH : Signal Transduction, Mitogen-Activated Protein Kinase Kinases, MESH : Mitogen-Activated Protein Kinases, Cell Biology, Molecular biology, MESH : Rats, Sprague-Dawley, Corpus Striatum, Rats, Kinetics, MESH : Proto-Oncogene Proteins c-fos, MESH : Brain, Gene Expression Regulation, [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Calcium-Calmodulin-Dependent Protein Kinases, biology.protein, MESH : Animals, MESH : ets-Domain Protein Elk-1, Extracellular Space, 030217 neurology & neurosurgery, Transcription Factors
Abstract: International audience; In cell culture systems, the TCF Elk-1 represents a convergence point for extracellular signal-related kinase (ERK) and c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) subclasses of mitogen-activated protein kinase (MAPK) cascades. Its phosphorylation strongly potentiates its ability to activate transcription of the c-fos promoter through a ternary complex assembled on the c-fos serum response element. In rat brain postmitotic neurons, Elk-1 is strongly expressed (V. Sgambato, P. Vanhoutte, C. Pagès, M. Rogard, R. A. Hipskind, M. J. Besson, and J. Caboche, J. Neurosci. 18:214-226, 1998). However, its physiological role in these postmitotic neurons remains to be established. To investigate biochemically the signaling pathways targeting Elk-1 and c-fos in mature neurons, we used a semi-in vivo system composed of brain slices stimulated with the excitatory neurotransmitter glutamate. Glutamate treatment leads to a robust, progressive activation of the ERK and JNK/SAPK MAPK cascades. This corresponds kinetically to a significant increase in Ser383-phosphorylated Elk-1 and the appearance of c-fos mRNA. Glutamate also causes increased levels of Ser133-phosphorylated cyclic AMP-responsive element-binding protein (CREB) but only transiently relative to Elk-1 and c-fos. ERK and Elk-1 phosphorylation are blocked by the MAPK kinase inhibitor PD98059, indicating the primary role of the ERK cascade in mediating glutamate signaling to Elk-1 in the rat striatum in vivo. Glutamate-mediated CREB phosphorylation is also inhibited by PD98059 treatment. Interestingly, KN62, which interferes with calcium-calmodulin kinase (CaM-K) activity, leads to a reduction of glutamate-induced ERK activation and of CREB phosphorylation. These data indicate that ERK functions as a common component in two signaling pathways (ERK/Elk-1 and ERK/?/CREB) converging on the c-fos promoter in postmitotic neuronal cells and that CaM-Ks act as positive regulators of these pathways.
Published: 1999
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43. Stat3 and Gfi-1 Transcription Factors Control Th17 Cell Immunosuppressive Activity via the Regulation of Ectonucleotidase Expression

Author: Bernhard Ryffel, Simon C. Robson, Sylvain Ladoire, Jean René Pallandre, François Ghiringhelli, Lionel Apetoh, Frédérique Végran, Aziz Hichami, Angélique Chevriaux, Gérard Eberl, Christophe Borg, Julie Vincent, Cédric Rébé, Grégoire Mignot, David Masson, Fanny Chalmin, Valentin Derangère, Mélanie Bruchard, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Department of Medicine and Surgery, Harvard Medical School [Boston] ( HMS ) -Beth Israel Deaconess Medical Centre-Liver Center and Transplantation Institute, Développement des Tissus Lymphoïdes, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), Immunologie et embryologie moléculaires ( IEM ), Université d'Orléans ( UO ) -Centre National de la Recherche Scientifique ( CNRS ), Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Harvard Medical School [Boston] (HMS)-Beth Israel Deaconess Medical Centre-Liver Center and Transplantation Institute, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Immunologie et Embryologie Moléculaires (IEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Saas, Philippe, Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), and Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]
Subjects: Adoptive cell transfer, MESH : Transcription Factors, Cellular differentiation, MESH: Th17 Cells, T-Lymphocytes, Cell, MESH : Promoter Regions, Genetic, MESH : RNA, Small Interfering, MESH: Mice, Knockout, Mice, 0302 clinical medicine, Transforming Growth Factor beta, MESH: RNA, Small Interfering, MESH : STAT3 Transcription Factor, Immunology and Allergy, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Ectonucleotidase, MESH: Animals, RNA, Small Interfering, STAT3, MESH: Lymphocytes, Tumor-Infiltrating, Promoter Regions, Genetic, MESH: Antigens, CD, 5'-Nucleotidase, Regulation of gene expression, Mice, Knockout, 0303 health sciences, MESH : Gene Expression Regulation, Apyrase, MESH: STAT3 Transcription Factor, MESH: Transcription Factors, MESH: Gene Expression Regulation, MESH : Mice, Transgenic, Cell biology, MESH : Lymphocytes, Tumor-Infiltrating, DNA-Binding Proteins, MESH : Apyrase, Infectious Diseases, medicine.anatomical_structure, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH : DNA-Binding Proteins, MESH: Apyrase, STAT3 Transcription Factor, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH : Interleukin-6, MESH: Mice, Transgenic, T cell, Immunology, Mice, Transgenic, MESH : Mice, Inbred C57BL, Biology, 03 medical and health sciences, Lymphocytes, Tumor-Infiltrating, MESH: Mice, Inbred C57BL, Antigens, CD, MESH: Promoter Regions, Genetic, MESH : 5'-Nucleotidase, MESH : Mice, medicine, MESH : Antigens, CD, MESH : Th17 Cells, Animals, Transcription factor, MESH: Mice, MESH: Transforming Growth Factor beta, 030304 developmental biology, MESH : T-Lymphocytes, Binding Sites, Interleukin-6, MESH: Interleukin-6, Mice, Inbred C57BL, MESH: T-Lymphocytes, MESH : Transforming Growth Factor beta, MESH: Binding Sites, Gene Expression Regulation, biology.protein, MESH : Mice, Knockout, Th17 Cells, MESH : Animals, MESH: 5'-Nucleotidase, MESH: DNA-Binding Proteins, MESH : Binding Sites, 030215 immunology, Transcription Factors
Abstract: International audience; Although Th17 cells are known to promote tissue inflammation and autoimmunity, their role during cancer progression remains elusive. Here, we showed that in vitro Th17 cells generated with the cytokines IL-6 and TGF-β expressed CD39 and CD73 ectonucleotidases, leading to adenosine release and the subsequent suppression of CD4(+) and CD8(+) T cell effector functions. The IL-6-mediated activation of the transcription factor Stat3 and the TGF-β-driven downregulation of Gfi-1 transcription factor were both essential for the expression of ectonucleotidases during Th17 cell differentiation. Stat3 supported whereas Gfi-1 repressed CD39 and CD73 expression by binding to their promoters. Accordingly, Th17 cells differentiated with IL-1β, IL-6, and IL-23 but without TGF-β did not express ectonucleotidases and were not immunosuppressive. Finally, adoptive transfer of Th17 cells induced by TGF-β and IL-6 promoted tumor growth in a CD39-dependent manner. Thus, ectonucleotidase expression supports the immunosuppressive fate of Th17 cells in cancer.
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44. JunD Reduces Tumor Angiogenesis by Protecting Cells from Oxidative Stress

Author: Jacques Pouysségur, Damien Gerald, Denise A. Chan, Fatima Mechta-Grigoriou, Amato J. Giaccia, Moshe Yaniv, Edurne Berra, Daniel Mansuy, Yves Frapart, Expression Génétique et Maladies, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Institut de signalisation, biologie du développement et cancer ( ISBDC ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques ( LCBPT - UMR 8601 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Centre National de la Recherche Scientifique ( CNRS ), Dept of Radiation Oncology, Stanford University [Stanford], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut de signalisation, biologie du développement et cancer (ISBDC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Department of Radiation Oncology [Stanford], Stanford Medicine, Stanford University-Stanford University, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), and Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Vascular Endothelial Growth Factor A, MESH : Oxidative Stress, MESH : Transcription Factors, Proto-Oncogene Proteins c-jun, Angiogenesis, Cell, MESH : Reactive Oxygen Species, medicine.disease_cause, Antioxidants, MESH : Iron, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Neovascularization, 0302 clinical medicine, Neoplasms, MESH: Up-Regulation, MESH: Animals, MESH: Neoplasms, MESH : Up-Regulation, G alpha subunit, chemistry.chemical_classification, Regulation of gene expression, MESH: Iron, 0303 health sciences, MESH: Oxidative Stress, MESH : Procollagen-Proline Dioxygenase, Neovascularization, Pathologic, integumentary system, MESH: Reactive Oxygen Species, MESH: Transcription Factors, MESH: Gene Expression Regulation, Neoplastic, Up-Regulation, Cell biology, Gene Expression Regulation, Neoplastic, medicine.anatomical_structure, 030220 oncology & carcinogenesis, MESH : Vascular Endothelial Growth Factor A, MESH: Hydrogen Peroxide, MESH : Antioxidants, medicine.symptom, MESH: ras Proteins, MESH : Proto-Oncogene Proteins c-jun, MESH: Procollagen-Proline Dioxygenase, MESH : Hypoxia-Inducible Factor 1, alpha Subunit, MESH : Gene Expression Regulation, Neoplastic, Iron, Procollagen-Proline Dioxygenase, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, MESH: Hypoxia-Inducible Factor 1, alpha Subunit, General Biochemistry, Genetics and Molecular Biology, Dioxygenases, Hypoxia-Inducible Factor-Proline Dioxygenases, 03 medical and health sciences, MESH : Dioxygenases, MESH: Dioxygenases, medicine, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Transcription factor, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, Reactive oxygen species, MESH: Humans, MESH: Proto-Oncogene Proteins c-jun, Biochemistry, Genetics and Molecular Biology(all), MESH: Vascular Endothelial Growth Factor A, MESH: Antioxidants, MESH : Humans, MESH : Neovascularization, Pathologic, Hydrogen Peroxide, Hypoxia-Inducible Factor 1, alpha Subunit, Molecular biology, MESH : Neoplasms, Oxidative Stress, chemistry, ras Proteins, MESH : Animals, MESH : Hydrogen Peroxide, MESH : ras Proteins, Reactive Oxygen Species, MESH: Neovascularization, Pathologic, Oxidative stress, Transcription Factors
Abstract: International audience; Reactive oxygen species (ROS) are implicated in the pathophysiology of various diseases, including cancer. In this study, we show that JunD, a member of the AP-1 family of transcription factors, reduces tumor angiogenesis by limiting Ras-mediated production of ROS. Using junD-deficient cells, we demonstrate that JunD regulates genes involved in antioxidant defense, H2O2 production, and angiogenesis. The accumulation of H2O2 in junD-/- cells decreases the availability of FeII and reduces the activity of HIF prolyl hydroxylases (PHDs) that target hypoxia-inducible factors-alpha (HIFalpha) for degradation. Subsequently, HIF-alpha proteins accumulate and enhance the transcription of VEGF-A, a potent proangiogenic factor. Our study uncovers the mechanism by which JunD protects cells from oxidative stress and exerts an antiangiogenic effect. Furthermore, we provide new insights into the regulation of PHD activity, allowing immediate reactive adaptation to changes in O2 or iron levels in the cell.
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