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1. The Landscape of L1 Retrotransposons in the Human Genome Is Shaped by Pre-insertion Sequence Biases and Post-insertion Selection

Author

Simona Saccani, Marc Bailly-Bechet, Dominic van Essen, Nicolas Gilbert, Oliver Siol, Pilvi Nigumann, Tania Sultana, Léo Pioger, Amal Zine El Aabidine, Claude Philippe, Jean-Christophe Andrau, Gaël Cristofari, Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université Côte d'Azur (UCA), Institut Gilbert-Laustriat : Biomolécules, Biotechnologie, Innovation Thérapeutique, Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique Moléculaire de Montpellier (IGMM), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Fondation pour la Recherche Medicale [FRM-DEP20131128533], European Research Council [ERC-2009-StG 243312], Agence Nationale de la Recherche (LABEX SIGNALIFE) [ANR-11-LABX-0028-01], Agence Nationale de la Recherche (RETROMET) [ANR-16-CE12-0020], Canceropole PACA (Projet Emergence), CNRS [GDR 3546], University Hospital Federation (FHU) OncoAge, FEDER, Inserm, Universite Cote d'Azur (France), University of Dhaka (Bangladesh), Agence Nationale de la Recherche (RETROGENO) [ANR-12-BSV6-0003], Region Provence Alpes Cote d'Azur, Conseil Departemental 06, ITMO Cancer Aviesan [plan cancer], ANR: 11-LABX-0028,SIGNALIFE,program 'Investments for the Future' LABEX SIGNALIFE, ANR-16-CE12-0020,RETROMET,Rendre unique l'ADN répété ou comment révéler la régulation épigénétique des rétrotransposons L1 dans les cellules somatiques humaines à une résolution inégalée.(2016), ANR-12-BSV6-0003,RETROGENO,Complexes de rétrotransposition du LINE-1 humain et instabilité génomique(2012), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Institut Sophia Agrobiotech (ISA), 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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Côte d'Azur (UCA), ANR-11-LABX-0028,SIGNALIFE,Réseau d'Innovation sur les Voies de Signalisation en Sciences de la Vie(2011), CCSD, Accord Elsevier, Centres d'excellences - Réseau d'Innovation sur les Voies de Signalisation en Sciences de la Vie - - SIGNALIFE2011 - ANR-11-LABX-0028 - LABX - VALID, Rendre unique l'ADN répété ou comment révéler la régulation épigénétique des rétrotransposons L1 dans les cellules somatiques humaines à une résolution inégalée. - - RETROMET2016 - ANR-16-CE12-0020 - AAPG2016 - VALID, BLANC - Complexes de rétrotransposition du LINE-1 humain et instabilité génomique - - RETROGENO2012 - ANR-12-BSV6-0003 - BLANC - VALID, Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA), and Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)

Subjects
DNA Replication, replication, Retroelements, [SDV]Life Sciences [q-bio], x-chromosome incactivation, Retrotransposon, Biology, dna, Genome, 03 medical and health sciences, 0302 clinical medicine, read alignement, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Insertion sequence, Molecular Biology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Whole genome sequencing, 0303 health sciences, Replication timing, Natural selection, Genome, Human, line-1 retrotransposition, Chromosome Mapping, Genomics, Cell Biology, LINE1, reverse transcription, [SDV] Life Sciences [q-bio], Long Interspersed Nucleotide Elements, Evolutionary biology, DNA Transposable Elements, human-cells, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Human genome, Mobile genetic elements, transposable elements, rplication, reveals, intergration site selection, 030217 neurology & neurosurgery, HeLa Cells
Abstract

International audience; L1 retrotransposons are transposable elements and major contributors of genetic variation in humans. Where L1 integrates into the genome can directly impact human evolution and disease. Here, we experimentally induced L1 retrotransposition in cells and mapped integration sites at nucleotide resolution. At local scales, L1 integration is mostly restricted by genome sequence biases and the specificity of the L1 machinery. At regional scales, L1 shows a broad capacity for integration into all chromatin states, in contrast to other known mobile genetic elements. However, integration is influenced by the replication timing of target regions, suggesting a link to host DNA replication. The distribution of new L1 integrations differs from those of preexisting L1 copies, which are significantly reshaped by natural selection. Our findings reveal that the L1 machinery has evolved to efficiently target all genomic regions and underline a predominant role for post-integrative processes on the distribution of endogenous L1 elements.

Published
2019

2. DNA helicase RecQ1 regulates mutually exclusive expression of virulence genes in Plasmodium falciparum via heterochromatin alteration

Author

Xueyu Dai, Shigang Yin, Zhou Li, Xiu Cheng, Jun Miao, Maoxin Sun, Nicolas Gilbert, Lubin Jiang, Jieqiong Wei, Zhenghui Huang, Liwang Cui, Institut Pasteur de Shanghai, Académie des Sciences de Chine - Chinese Academy of Sciences (IPS-CAS), Réseau International des Instituts Pasteur (RIIP), ShanghaiTech University [Shanghai], Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Morsani College of Medicine [Tampa, USA], University of South Florida [Tampa] (USF), Key Laboratory of Molecular Virology & Immunology (LMVI), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Grant support R01 AI116466/AI/NIAID NIH HHS/United States U19 AI089672/AI/NIAID NIH HHS/United States, Hennaut, Odile, and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)

Subjects
Genetics, 0303 health sciences, virulence gene, Multidisciplinary, biology, Heterochromatin, [SDV]Life Sciences [q-bio], 030302 biochemistry & molecular biology, Plasmodium falciparum, heterochromatin, Helicase, DNA helicases, Subtelomere, [SDV] Life Sciences [q-bio], Complementation, mutually exclusive expression, 03 medical and health sciences, Transcription (biology), biology.protein, Gene silencing, Gene family, Gene, 030304 developmental biology
Abstract

The Plasmodium falciparum var gene family encodes ∼60 surface antigens by which parasites escape the host immune responses via clonal expression of var genes. However, the mechanism controlling this mutual exclusivity, associated with alterations in chromatin assembly, is not understood. Here, we determined how expression of the var gene family is regulated by two RecQ DNA helicase family members, PfRecQ1 and PfWRN, in P. falciparum . Through genetic manipulation, we found that the complete var repertoire was silenced on PfRecQ1 knockout, whereas their expression did not show noticeable changes when PfWRN was knocked out. More important, mutually exclusive expression of var genes could be rescued by complementation of PfRecQ1. In addition, knocking out either of these two helicase genes changed the perinuclear cluster distribution of subtelomeres and subtelomeric var genes. Whereas deletion of PfRecQ1 increased the heterochromatin mark trimethylated (H3K9me3) at the transcription start site (TSS) of the var gene upsC1 , that deletion had no effect on the global distribution of H3K9me3 over gene bodies, including those for the var genes. ChIP-seq assay showed that PfRecQ1 was enriched globally at the TSSs of all genes, whereas PfWRN-enriched regions occurred at the gene bodies of the var gene family, but not of other genes or at TSSs of all genes. On PfRecQ1 deletion, the upsC1 var gene moved from the active perinuclear transcription region to a silenced region of the upsC type. These findings imply that PfRecQ1, but not PfWRN, is essential for maintaining the clonal expression of var genes.

Published
2019

3. Images des Américains dans la Grande Guerre. De la Bretagne au front de l'Ouest

Author

Joret, Eric, Nicolas, Gilbert, Kowalski, Jean-Marie, Histoire et Archéologie maritimes (HAM), Musée National de la Marine de Paris-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Ecole Navale (EN)-Musée National de la Marine de Paris-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
bretagne, united states, Etats-Unis, Première Guerre mondiale, grande guerre, great war, brittany, [SHS.HIST]Humanities and Social Sciences/History, ComputingMilieux_MISCELLANEOUS, first world war, [SHS]Humanities and Social Sciences
Abstract

International audience

Published
2017

4. New chimeric RNAs in acute myeloid leukemia

Author

Anne Laure Bougé, Anthony Boureux, Sacha Beaumeunier, Sébastien Riquier, Jean-Baptiste Gaillard, Nicolas Gilbert, Jean-Marc Lemaitre, Nicolas Philippe, Jérôme Audoux, Andre Megarbane, Delphine Bacq-Daian, Ronnie Alves, Christine Chomienne, Thérèse Commes, Florence Ruffle, Elias Bou Samra, Bruno Cassinat, Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Université Paris-Saclay, Institut Curie [Paris], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hémopathies Myéloïdes : Cellules Souches, Modèles Pré-Cliniques et Recherche Translationnelle (UMR 1131), Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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, Philips, Alexandre, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)

Subjects
0301 basic medicine, bioinformatics analysis, chimeric RNA, [SDV]Life Sciences [q-bio], Computational biology, acute myeloid leukemia, Biology, Leukemia & Proliferative Disorders of Hematic Cells, Bioinformatics, DNA sequencing, General Biochemistry, Genetics and Molecular Biology, Exon, 03 medical and health sciences, 0302 clinical medicine, Chimeric RNA, medicine, splice, Classification (CRAC), PML-RARA, General Pharmacology, Toxicology and Pharmaceutics, Gene, ComputingMilieux_MISCELLANEOUS, General Immunology and Microbiology, TRIM28, biomarkers, Myeloid leukemia, Articles, General Medicine, RNAseq, medicine.disease, Complex Read Analysis, 3. Good health, [SDV] Life Sciences [q-bio], Leukemia, 030104 developmental biology, RNA editing, 030220 oncology & carcinogenesis, Research Article
Abstract

Background: High-throughput next generation sequencing (NGS) technologies enable the detection of biomarkers used for tumor classification, disease monitoring and cancer therapy. Whole-transcriptome analysis using RNA-seq is important, not only as a means of understanding the mechanisms responsible for complex diseases but also to efficiently identify novel genes/exons, splice isoforms, RNA editing, allele-specific mutations, differential gene expression and fusion-transcripts or chimeric RNA (chRNA). Methods: We used Crac, a tool that uses genomic locations and local coverage to classify biological events and directly infer splice and chimeric junctions within a single read. Crac’s algorithm extracts transcriptional chimeric events irrespective of annotation with a high sensitivity, and CracTools was used to aggregate, annotate and filter the chRNA reads. The selected chRNA candidates were validated by real time PCR and sequencing. In order to check the tumor specific expression of chRNA, we analyzed a publicly available dataset using a new tag search approach. Results: We present data related to acute myeloid leukemia (AML) RNA-seq analysis. We highlight novel biological cases of chRNA, in addition to previously well characterized leukemia chRNA. We have identified and validated 17 chRNAs among 3 AML patients: 10 from an AML patient with a translocation between chromosomes 15 and 17 (AML-t(15;17), 4 from patient with normal karyotype (AML-NK) 3 from a patient with chromosomal 16 inversion (AML-inv16). The new fusion transcripts can be classified into four groups according to the exon organization. Conclusions: All groups suggest complex but distinct synthesis mechanisms involving either collinear exons of different genes, non-collinear exons, or exons of different chromosomes. Finally, we check tumor-specific expression in a larger RNA-seq AML cohort and identify new AML biomarkers that could improve diagnosis and prognosis of AML.

Published
2017

5. International Congress on Transposable elements (ICTE 2016) in Saint Malo: mobile elements under the sun of Brittany

Author

Mireille Bétermier, Jean-Nicolas Volff, Chantal Vaury, Michael Chandler, Antoine Bridier-Nahmias, Pascale Lesage, Gaël Cristofari, Nicolas Gilbert, Hadi Quesneville, Séverine Chambeyron, Pathologie cellulaire : aspects moléculaires et viraux / Pathologie et Virologie Moléculaire, Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), 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), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Laboratoire de microbiologie et génétique moléculaires - UMR5100 (LMGM), Centre de Biologie Intégrative (CBI), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Unité de Recherche Génomique Info (URGI), Institut National de la Recherche Agronomique (INRA), Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Institut de Génomique Fonctionnelle de Lyon (IGFL), École normale supérieure de Lyon (ENS de Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut Universitaire d'Hématologie ( IUH ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Sud - Paris 11 ( UP11 ), Département chimie alimentation santé environnement risque-CNAM ( CASER ), Laboratoire de microbiologie et génétique moléculaires ( LMGM ), Université Paul Sabatier - Toulouse 3 ( UPS ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de génétique humaine ( IGH ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Recherche sur le Cancer et le Vieillissement ( IRCAN ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), CHU Saint-Eloi-Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Unité de Recherche Génomique Info ( URGI ), Institut National de la Recherche Agronomique ( INRA ), Génétique, reproduction et développement ( GReD ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR79-Université d'Auvergne - Clermont-Ferrand I ( UdA ) -Université Blaise Pascal - Clermont-Ferrand 2 ( UBP ), Institut de Génomique Fonctionnelle de Lyon ( IGFL ), École normale supérieure - Lyon ( ENS Lyon ) -Institut National de la Recherche Agronomique ( INRA ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-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 microbiologie et génétique moléculaires (LMGM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA), Génétique, Reproduction et Développement - Clermont Auvergne (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Lyon (ENS Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), 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)-Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis (... - 2019) (UNS), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-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 Recherche Agronomique (INRA)-École normale supérieure - Lyon (ENS Lyon), Lesage, Pascale, and BMC, BMC

Subjects
0301 basic medicine, Transposable element, lcsh:QH426-470, Evolution of transposable elements, [SDV]Life Sciences [q-bio], education, Control of transposition, Library science, Impact on genomes, Meeting Report, Biology, Mobile DNA, 03 medical and health sciences, Human health, International congress, Molecular Biology, Malo, ComputingMilieux_MISCELLANEOUS, Genetics, [ SDV ] Life Sciences [q-bio], Mechanism of transposition, SAINT, Genome structure, biology.organism_classification, [SDV] Life Sciences [q-bio], lcsh:Genetics, 030104 developmental biology, Transposon-based gene therapy, Transposable elements, Mobile genetic elements
Abstract

International audience; AbstractThe third international conference on Transposable Elements (ICTE) was held 16–19 April 2016 in Saint Malo, France. Organized by the French Transposition Community (Research group of the CNRS: “Mobile genetic elements: from mechanism to populations, an integrative approach”) and the French Society of Genetics, the conference’s goal was to bring together researchers who study transposition in diverse organisms, using multiple experimental approaches. The meeting gathered 180 participants from all around the world. Most of them contributed through poster presentations, invited talks and short talks selected from poster abstracts. The talks were organized into six scientific sessions: “Taming mobile DNA: self and non-self recognition”; “Trans-generational inheritance”; “Mobile DNA genome structure and organization, from molecular mechanisms to applications”; “Remembrance of (retro)transposon past: mobile DNA in genome evolution”; and finally “The yin and the yang of mobile DNA in human health”.

Published
2016

6. Cellular Localization of Engineered Human LINE-1 RNA and Proteins

Author

Aurélien J. Doucet, Nicolas Gilbert, Eugenia Basyuk, Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), We are grateful to Edouard Bertrand (CNRS, Institut de Genetique Moleculaire de Montpellier, France) for the gift of plasmids, probes, and sharing protocols. We thank Robert Singer (Albert Einstein College of Medicine, Yeshiva University, USA) for sharing online protocols (available at http://www.singerlab.org/protocols) and John V. Moran (Department of Human Genetics, University of Michigan, USA) for sharing plasmids. We are grateful to Nicole Lautredou at Montpellier RIO Imaging, France. This work was supported by the Institut National de la Santé Et de la Recherche Médicale (INSERM), the Centre National de la Recherche Scientifique (CNRS) and the Agence Nationale de la Recherche (ANR-12-BSV6-0003, RETROGENO) [to NG], Ministère de l’Enseignement Supérieur et de la Recherche, Association pour la Recherche contre le Cancer (ARC), and Fondation Recherche Médicale (FRM) [doctoral fellowships to AJD].Reference, Jose L. Garcia-Pérez, and ANR-12-BSV6-0003,RETROGENO,Complexes de rétrotransposition du LINE-1 humain et instabilité génomique(2012)

Subjects
0301 basic medicine, Messenger RNA, MS2 fluorescent in situ hybridization, medicine.diagnostic_test, [SDV]Life Sciences [q-bio], Immunofluorescence, RNA, Retrotransposon, Transfection, In situ hybridization, Biology, Subcellular localization, 3. Good health, Cell biology, 03 medical and health sciences, 030104 developmental biology, L1 mRNA, ORF1p, ORF2p, LINE-1 retrotransposon, medicine, Cellular localization
Abstract

International audience; The human LINE-1 retrotransposon has the ability to mobilize into a new genomic location through an intracellular replication cycle. Immunofluorescence and in situ hybridization experiments have been developed to detect subcellular localization of retrotransposition intermediates (i.e., ORF1p, ORF2p, and L1 mRNA). Currently, these protocols are also used to validate the interaction between retrotransposition complex components and potential cellular partners involved in L1 replication. Here, we describe in details methods for the identification of LINE-1 proteins and/or RNA in cells transfected with vectors expressing engineered human LINE-1 elements.

Published
2016

7. U6 snRNA Pseudogenes: Markers of Retrotransposition Dynamics in Mammals

Author

Aurélien J. Doucet, Oliver Siol, Nicolas Gilbert, Jérôme Audoux, Gaëtan Droc, Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institute for Research on Cancer and Aging, Nice (IRCAN), INSERM, U1081, CNRS UMR 7284, Nice, Amélioration génétique et adaptation des plantes méditerranéennes et tropicales (UMR AGAP), Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Institut National de la Recherche Agronomique (INRA)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), The authors thank Lise Corriger, Marjorie Côte, SandrineEnjalbert, and Oussama Meziane for their help in the initialscreening of snRNA sequences, Ned Lamb and NicolasPhilippe for helpful discussion, Guillaume Gielly, JacquesFaure and Alfred Vriese, members of the computing facilityat the Institute of Human Genetics, for their help with com-puters and servers. A.J.D. was the recipient of fellowshipsfrom the French government (Ministe`re de l’EnseignementSuperieur et de la Recherche), from Association pour laRecherche contre le Cancer (ARC), and from Fondationpour la Recherche Medicale(FRM).O.S.wastherecipientof a fellowship from the Deutsche Forschungsgemeinschaft(DFG). J.A. was the recipient of a fellowship from FRM. Workin the laboratory of N.G. is supported by the Institut Nationalde la SanteEtdelaRechercheMedicale (INSERM), theCentre National de Recherche Scientifique (CNRS), and theAgence Nationale de la Recherche (ANR-12-BSV6-0003,RETROGENO)., ANR-12-BSV6-0003,RETROGENO,Complexes de rétrotransposition du LINE-1 humain et instabilité génomique(2012), Larose, Catherine, and BLANC - Complexes de rétrotransposition du LINE-1 humain et instabilité génomique - - RETROGENO2012 - ANR-12-BSV6-0003 - BLANC - VALID

Subjects
Transposable element, small nuclear RNA, Retroelements, Polyadenylation, Pseudogene, Molecular Sequence Data, Retrotransposon, [SDV.GEN] Life Sciences [q-bio]/Genetics, Computational biology, Biology, Séquence d'ARN, Genome, génomique, Pseudogène, RNA, Small Nuclear, Genetics, Animals, Humans, Molecular Biology, Discoveries, Ecology, Evolution, Behavior and Systematics, ComputingMilieux_MISCELLANEOUS, long interspersed nuclear element, Mammals, [SDV.GEN]Life Sciences [q-bio]/Genetics, Base Sequence, Genome, Human, retrotransposon, Transposition de gènes, Templates, Genetic, L10 - Génétique et amélioration des animaux, ARN, Long interspersed nuclear element, Long Interspersed Nucleotide Elements, Human genome, Mammifère, Pseudogenes, Small nuclear RNA
Abstract

Supplementary Material : Supplementary tables S1–S3andfigure S1areavailableatMolecular Biology and Evolutiononline (http://www.mbe.oxfordjournals.org/).; International audience; Transposable elements comprise more than 45% of the human genome and long interspersed nuclear element 1 (LINE-1 or L1) is the only autonomous mobile element remaining active. Since its identification, it has been proposed that L1 contributes to the mobilization and amplification of other cellular RNAs and more recently, experimental demonstrations of this function has been described for many transcripts such as Alu, a nonautonomous mobile element, cellular mRNAs, or small noncoding RNAs. Detailed examination of the mobilization of various cellular RNAs revealed distinct pathways by which they could be recruited during retrotransposition; template choice or template switching. Here, by analyzing genomic structures and retrotransposition signatures associated with small nuclear RNA (snRNA) sequences, we identified distinct recruiting steps during the L1 retrotransposition cycle for the formation of snRNA-processed pseudogenes. Interestingly, some of the identified recruiting steps take place in the nucleus. Moreover, after comparison to other vertebrate genomes, we established that snRNA amplification by template switching is common to many LINE families from several LINE clades. Finally, we suggest that U6 snRNA copies can serve as markers of L1 retrotransposition dynamics in mammalian genomes.

Published
2015

8. Leucine-Rich Repeat Receptor Kinases are sporadically distributed in eukaryotic genomes

Author

Christophe Périn, Gaëtan Droc, Mathieu Gourgues, Agnès Attard, Anne Dievart, Nicolas Gilbert, Emmanuel Guiderdoni, Amélioration génétique et adaptation des plantes méditerranéennes et tropicales (UMR AGAP), Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Institut National de la Recherche Agronomique (INRA)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), This research was funded by the French Agence Nationale de la Recherche, Dievart, Anne, Institut National de la Recherche Agronomique (INRA)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)

Subjects
H01 - Protection des végétaux - Considérations générales, 0106 biological sciences, genetics and heredity, plant, phylogeny, 01 natural sciences, Genome, F30 - Génétique et amélioration des plantes, Sequence Analysis, Protein, ComputingMilieux_MISCELLANEOUS, Oomycete, Genetics, 0303 health sciences, Phylogenetic tree, biology, Eukaryota, Plants, arabidopsis, proteins, genome, sequence alignment, evolutionary biology, Oomycetes, Plante, Genome, Plant, Research Article, Evolution, Sequence alignment, Transférase, Leucine-rich repeat, Evolution, Molecular, 03 medical and health sciences, Leucine, Phylogenetics, QH359-425, Gene family, Gene, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, Génie génétique, [SDV.GEN]Life Sciences [q-bio]/Genetics, Génome, fungi, biology.organism_classification, Evolutionary biology, Protein Kinases, 010606 plant biology & botany
Abstract

Background Plant leucine-rich repeat receptor-like kinases (LRR-RLKs) are receptor kinases that contain LRRs in their extracellular domain. In the last 15 years, many research groups have demonstrated major roles played by LRR-RLKs in plants during almost all developmental processes throughout the life of the plant and in defense/resistance against a large range of pathogens. Recently, a breakthrough has been made in this field that challenges the dogma of the specificity of plant LRR-RLKs. Results We analyzed ~1000 complete genomes and show that LRR-RK genes have now been identified in 8 non-plant genomes. We performed an exhaustive phylogenetic analysis of all of these receptors, revealing that all of the LRR-containing receptor subfamilies form lineage-specific clades. Our results suggest that the association of LRRs with RKs appeared independently at least four times in eukaryotic evolutionary history. Moreover, the molecular evolutionary history of the LRR-RKs found in oomycetes is reminiscent of the pattern observed in plants: expansion with amplification/deletion and evolution of the domain organization leading to the functional diversification of members of the gene family. Finally, the expression data suggest that oomycete LRR-RKs may play a role in several stages of the oomycete life cycle. Conclusions In view of the key roles that LRR-RLKs play throughout the entire lifetime of plants and plant-environment interactions, the emergence and expansion of this type of receptor in several phyla along the evolution of eukaryotes, and particularly in oomycete genomes, questions their intrinsic functions in mimicry and/or in the coevolution of receptors between hosts and pathogens.

Published
2011

9. Les recteurs de la monarchie de Juillet (1830-1848)

Author

Nicolas, Gilbert, Centre de Recherches Historiques de l'Ouest (CERHIO), Le Mans Université (UM)-Université d'Angers (UA)-Université de Bretagne Sud (UBS)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), Condette Jean-François, and Le Goherel Henri

Subjects
Bretagne (France), 19e siècle, Recteurs d'académie, France, Enseignement, [SHS.HIST]Humanities and Social Sciences/History
Published
2008

10. Distinct mechanisms for trans-mediated mobilization of cellular RNAs by the LINE-1 reverse transcriptase

Author

Alain Bucheton, Aurélien J. Doucet, John V. Moran, Jose L. Garcia-Perez, Nicolas Gilbert, Institut de génétique humaine (IGH), and Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Genome evolution, RNA, Untranslated, Letter, Sequence analysis, Retrotransposon, Biology, Indirect evidence, 03 medical and health sciences, 0302 clinical medicine, RNA, Small Nuclear, Genetics, Humans, Genetics (clinical), ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, [SDV.GEN]Life Sciences [q-bio]/Genetics, Sequence Analysis, RNA, RNA-Directed DNA Polymerase, fungi, RNA, food and beverages, Computational Biology, Reverse transcriptase, Cell biology, Long Interspersed Nucleotide Elements, 030217 neurology & neurosurgery, Small nuclear RNA, HeLa Cells
Abstract

Long Interspersed Element-1 (LINE-1 or L1) sequences comprise ∼17% of human DNA and ongoing L1 retrotransposition continues to impact genome evolution. The L1-encoded proteins also can mobilize other cellular RNAs (e.g., Alu retrotransposons, SVA retrotransposons, and U6 snRNAs), which comprise ∼13% of human DNA. Here, we demonstrate that the trans-mediated mobilization of non-L1 RNAs can occur by either template choice or template-switching mechanisms. Remarkably, these mechanisms are not mutually exclusive, as both processes can operate sequentially on the same RNA template. Finally, we provide evidence that efficient U6 snRNA retrotransposition requires both ORF1p and ORF2p, providing indirect evidence for the action of ORF1p in U6 snRNA retrotransposition. Thus, we propose that the LINE-1-encoded reverse transcriptase can mediate the retrotransposition of non-L1 RNAs by distinct mechanisms.

Published
2007

11. Le temps de l'école (1880-1960)

Author

Nicolas, Gilbert, Luc, Jean-Noël, Centre de Recherches Historiques de l'Ouest (CERHIO), Le Mans Université (UM)-Université d'Angers (UA)-Université de Bretagne Sud (UBS)-Université de Rennes 2 (UR2), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)

Subjects
19e siècle, Ouvrages illustrés, France, 20e siècle, Enseignement, [SHS.HIST]Humanities and Social Sciences/History
Published
2006

12. La généralisation des écoles primaires: des innovations au repli (1830-1838)

Author

Nicolas, Gilbert, Centre de Recherches Historiques de l'Ouest (CERHIO), Le Mans Université (UM)-Université d'Angers (UA)-Université de Bretagne Sud (UBS)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), Harismendy Patrick, and Kalifa, Dominique

Subjects
19e siècle, Ecoles normales, France, [SHS.HIST]Humanities and Social Sciences/History, ComputingMilieux_MISCELLANEOUS, Enseignement primaire
Abstract

International audience

Published
2005

13. L'Etat, l'Eglise et l'école idéale: les représentations des instituteurs bretons sous le Second Empire

Author

Nicolas, Gilbert, Centre de Recherches Historiques de l'Ouest (CERHIO), Le Mans Université (UM)-Université d'Angers (UA)-Université de Bretagne Sud (UBS)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), Balcou Jean, Provost Georges, and Tranvouez Yvon

Subjects
Bretagne (France), 19e siècle, Politique religieuse, Professeurs des écoles, [SHS.HIST]Humanities and Social Sciences/History, Instituteurs, ComputingMilieux_MISCELLANEOUS, Enseignement primaire
Abstract

International audience

Published
2005

14. La fête de la jeunesse de Rennes (1925-2000)

Author

Nicolas, Gilbert, Centre de Recherches Historiques de l'Ouest (CERHIO), Le Mans Université (UM)-Université d'Angers (UA)-Université de Bretagne Sud (UBS)-Université de Rennes 2 (UR2), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Bretagne (France), Enfance, Rennes (Ille-et-Vilaine), Patronages, 20e siècle, jeunesse, [SHS.HIST]Humanities and Social Sciences/History, ComputingMilieux_MISCELLANEOUS
Abstract

National audience

Published
2005

15. Les instituteurs et la maison d'école rurale, dans l'Ouest au XIXe siècle

Author

Nicolas, Gilbert, Centre de Recherches Historiques de l'Ouest (CERHIO), Le Mans Université (UM)-Université d'Angers (UA)-Université de Bretagne Sud (UBS)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), Antoine Annie, Cocaud Martine, and Pichot Daniel

Subjects
19e siècle, Professeurs des écoles, Logements de fonction, France, Bretagne, [SHS.HIST]Humanities and Social Sciences/History, Instituteurs, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2002

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