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1. Chromatin-Based Classification of Genetically Heterogeneous AMLs into Two Distinct Subtypes with Diverse Stemness Phenotypes

Author

Yi, Guoqiang, Wierenga, Albertus T.J., Petraglia, Francesca, Narang, Pankaj, Janssen-Megens, Eva M., Mandoli, Amit, Merkel, Angelika, Berentsen, Kim, Kim, Bowon, Matarese, Filomena, Singh, Abhishek A., Habibi, Ehsan, Prange, Koen H.M., Mulder, André B., Jansen, Joop H., Clarke, Laura, Heath, Simon, van der Reijden, Bert A., Flicek, Paul, Yaspo, Marie-Laure, Gut, Ivo, Bock, Christoph, Schuringa, Jan Jacob, Altucci, Lucia, Vellenga, Edo, Stunnenberg, Hendrik G., and Martens, Joost H.A.

Published
2019
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2. The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease

Author

Astle, William J., Elding, Heather, Jiang, Tao, Allen, Dave, Ruklisa, Dace, Mann, Alice L., Mead, Daniel, Bouman, Heleen, Riveros-Mckay, Fernando, Kostadima, Myrto A., Lambourne, John J., Sivapalaratnam, Suthesh, Downes, Kate, Kundu, Kousik, Bomba, Lorenzo, Berentsen, Kim, Bradley, John R., Daugherty, Louise C., Delaneau, Olivier, Freson, Kathleen, Garner, Stephen F., Grassi, Luigi, Guerrero, Jose, Haimel, Matthias, Janssen-Megens, Eva M., Kaan, Anita, Kamat, Mihir, Kim, Bowon, Mandoli, Amit, Marchini, Jonathan, Martens, Joost H.A., Meacham, Stuart, Megy, Karyn, O’Connell, Jared, Petersen, Romina, Sharifi, Nilofar, Sheard, Simon M., Staley, James R., Tuna, Salih, van der Ent, Martijn, Walter, Klaudia, Wang, Shuang-Yin, Wheeler, Eleanor, Wilder, Steven P., Iotchkova, Valentina, Moore, Carmel, Sambrook, Jennifer, Stunnenberg, Hendrik G., Di Angelantonio, Emanuele, Kaptoge, Stephen, Kuijpers, Taco W., Carrillo-de-Santa-Pau, Enrique, Juan, David, Rico, Daniel, Valencia, Alfonso, Chen, Lu, Ge, Bing, Vasquez, Louella, Kwan, Tony, Garrido-Martín, Diego, Watt, Stephen, Yang, Ying, Guigo, Roderic, Beck, Stephan, Paul, Dirk S., Pastinen, Tomi, Bujold, David, Bourque, Guillaume, Frontini, Mattia, Danesh, John, Roberts, David J., Ouwehand, Willem H., Butterworth, Adam S., and Soranzo, Nicole

Published
2016
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3. β-Glucan Reverses the Epigenetic State of LPS-Induced Immunological Tolerance

Author

Novakovic, Boris, Habibi, Ehsan, Wang, Shuang-Yin, Arts, Rob J.W., Davar, Robab, Megchelenbrink, Wout, Kim, Bowon, Kuznetsova, Tatyana, Kox, Matthijs, Zwaag, Jelle, Matarese, Filomena, van Heeringen, Simon J., Janssen-Megens, Eva M., Sharifi, Nilofar, Wang, Cheng, Keramati, Farid, Schoonenberg, Vivien, Flicek, Paul, Clarke, Laura, Pickkers, Peter, Heath, Simon, Gut, Ivo, Netea, Mihai G., Martens, Joost H.A., Logie, Colin, and Stunnenberg, Hendrik G.

Published
2016
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4. Lineage-Specific Genome Architecture Links Enhancers and Non-coding Disease Variants to Target Gene Promoters

Author

Martens, Joost H., Kim, Bowon, Sharifi, Nilofar, Janssen-Megens, Eva M., Yaspo, Marie-Laure, Linser, Matthias, Kovacsovics, Alexander, Clarke, Laura, Richardson, David, Datta, Avik, Flicek, Paul, Javierre, Biola M., Burren, Oliver S., Wilder, Steven P., Kreuzhuber, Roman, Hill, Steven M., Sewitz, Sven, Cairns, Jonathan, Wingett, Steven W., Várnai, Csilla, Thiecke, Michiel J., Burden, Frances, Farrow, Samantha, Cutler, Antony J., Rehnström, Karola, Downes, Kate, Grassi, Luigi, Kostadima, Myrto, Freire-Pritchett, Paula, Wang, Fan, Stunnenberg, Hendrik G., Todd, John A., Zerbino, Daniel R., Stegle, Oliver, Ouwehand, Willem H., Frontini, Mattia, Wallace, Chris, Spivakov, Mikhail, and Fraser, Peter

Published
2016
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5. Epigenetic programming of monocyte-to-macrophage differentiation and trained innate immunity

Author

Saeed, Sadia, Quintin, Jessica, Kerstens, Hindrik H. D., Rao, Nagesha A., Aghajanirefah, Ali, Matarese, Filomena, Cheng, Shih-Chin, Ratter, Jacqueline, Berentsen, Kim, van der Ent, Martijn A., Sharifi, Nilofar, Janssen-Megens, Eva M., Ter Huurne, Menno, Mandoli, Amit, van Schaik, Tom, Ng, Aylwin, Burden, Frances, Downes, Kate, Frontini, Mattia, Kumar, Vinod, Giamarellos-Bourboulis, Evangelos J., Ouwehand, Willem H., van der Meer, Jos W. M., Joosten, Leo A. B., Wijmenga, Cisca, Martens, Joost H. A., Xavier, Ramnik J., Logie, Colin, Netea, Mihai G., and Stunnenberg, Hendrik G.

Published
2014

8. Molecular mechanism of anaerobic ammonium oxidation

Author

Kartal, Boran, Maalcke, Wouter J., de Almeida, Naomi M., Cirpus, Irina, Gloerich, Jolein, Geerts, Wim, Op den Camp, Huub J.M., Harhangi, Harry R., Janssen-Megens, Eva M., Francoijs, Kees-Jan, Stunnenberg, Hendrik G., Keltjens, Jan T., Jetten, Mike S.M., and Strous, Marc

Subjects
Physiological aspects, Research, Biogeochemical cycles -- Research, Oxidation-reduction reactions -- Research, Anaerobic bacteria -- Physiological aspects -- Research, Oxidation-reduction reaction -- Research
Abstract

Ammonium is difficult to activate in the absence of molecular oxygen. Therefore, how anammox bacteria are able to oxidize ammonium coupled to the reduction of nitrite and forge an N-N [...], Two distinct microbial processes, denitrification and anaerobic ammonium oxidation (anammox), are responsible for the release of fixed nitrogen as dinitrogen gas ([N.sub.2]) to the atmosphere (1-4). Denitrification has been studied for over 100 years and its intermediates and enzymes are well known (5). Even though anammox is a key biogeochemical process of equal importance, its molecular mechanism is unknown, but it was proposed to proceed through hydrazine ([N.sub.2][H.sub.4]) (6,7). Here we show that [N.sub.2][H.sub.4] is produced from the anammox substrates ammonium and nitrite and that nitric oxide (NO) is the direct precursor of [N.sub.2][H.sub.4]. We resolved the genes and proteins central to anammox metabolism and purified the key enzymes that catalyse [N.sub.2][H.sub.4] synthesis and its oxidation to [N.sub.2]. These results present a new biochemical reaction forging an N-N bond and fill a lacuna in our understanding of the biochemical synthesis of the [N.sub.2] in the atmosphere. Furthermore, they reinforce the role of nitric oxide in the evolution of the nitrogen cycle.

Published
2011
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9. Nitrite-driven anaerobic methane oxidation by oxygenic bacteria

Author

Ettwig, Katharina F., Butler, Margaret K., Paslier, Denis Le, Pelletier, Eric, Mangenot, Sophie, Kuypers, Marcel M.M., Schreiber, Frank, Dutilh, Bas E., Zedelius, Johannes, de Beer, Dirk, Gloerich, Jolein, Wessels, Hans J.C.T., van Alen, Theo, Luesken, Francisca, Wu, Ming L., van de Pas-Schoonen, Katinka T., Camp, Huub J.M. Op den, Janssen-Megens, Eva M., Francoijs, Kees-Jan, Stunnenberg, Henk, Weissenbach, Jean, Jetten, Mike S.M., and Strous, Marc

Subjects
Physiological aspects, Research, Denitrification -- Physiological aspects -- Research, Plant biochemistry -- Physiological aspects, Oxidation-reduction reactions -- Physiological aspects, Nitrous oxide -- Physiological aspects -- Research, Methane -- Physiological aspects -- Research, Phytochemistry -- Physiological aspects, Oxidation-reduction reaction -- Physiological aspects
Abstract

With the ubiquitous use of fertilizers in agriculture, nitrate (N[O.sub.3.sup.-]) and nitrite (N[O.sub.2.sup.-]) have become major electron acceptors in freshwater environments (1). The feedback of eutrophication on the atmospheric methane [...], Only three biological pathways are known to produce oxygen: photosynthesis, chlorate respiration and the detoxification of reactive oxygen species. Here we present evidence for a fourth pathway, possibly of considerable geochemical and evolutionary importance. The pathway was discovered after metagenomic sequencing of an enrichment culture that couples anaerobic oxidation of methane with the reduction of nitrite to dinitrogen. The complete genome of the dominant bacterium, named 'Candidatus Methylomirabilis oxyfera', was assembled. This apparently anaerobic, denitrifying bacterium encoded, transcribed and expressed the well-established aerobic pathway for methane oxidation, whereas it lacked known genes for dinitrogen production. Subsequent isotopic labelling indicated that 'M. oxyfera' bypassed the denitrification intermediate nitrous oxide by the conversion of two nitric oxide molecules to dinitrogen and oxygen, which was used to oxidize methane. These results extend our understanding of hydrocarbon degradation under anoxic conditions and explain the biochemical mechanism of a poorly understood freshwater methane sink. Because nitrogen oxides were already present on early Earth, our finding opens up the possibility that oxygen was available to microbial metabolism before the evolution of oxygenic photosynthesis.

Published
2010
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10. IMMUNOGENETICS: Epigenetic programming of monocyte-to-macrophage differentiation and trained innate immunity

Author

Saeed, Sadia, Quintin, Jessica, Kerstens, Hindrik H. D., Rao, Nagesha A., Aghajanirefah, Ali, Matarese, Filomena, Cheng, Shih-Chin, Ratter, Jacqueline, Berentsen, Kim, van der Ent, Martijn A., Sharifi, Nilofar, Janssen-Megens, Eva M., Huurne, Menno Ter, Mandoli, Amit, van Schaik, Tom, Ng, Aylwin, Burden, Frances, Downes, Kate, Frontini, Mattia, Kumar, Vinod, Giamarellos-Bourboulis, Evangelos J., Ouwehand, Willem H., van der Meer, Jos W. M., Joosten, Leo A. B., Wijmenga, Cisca, Martens, Joost H. A., Xavier, Ramnik J., Logie, Colin, Netea, Mihai G., and Stunnenberg, Hendrik G.

Published
2014
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12. The metagenome of the marine anammox bacterium ‘Candidatus Scalindua profunda’ illustrates the versatility of this globally important nitrogen cycle bacterium

Author

van de Vossenberg, Jack, Woebken, Dagmar, Maalcke, Wouter J., Wessels, Hans J. C. T., Dutilh, Bas E., Kartal, Boran, Janssen-Megens, Eva M., Roeselers, Guus, Yan, Jia, Speth, Daan, Gloerich, Jolein, Geerts, Wim, van der Biezen, Erwin, Pluk, Wendy, Francoijs, Kees-Jan, Russ, Lina, Lam, Phyllis, Malfatti, Stefanie A., Tringe, Susannah Green, Haaijer, Suzanne C. M., Op den Camp, Huub J. M., Stunnenberg, Henk G., Amann, Rudi, Kuypers, Marcel M. M., and Jetten, Mike S. M.

Published
2013
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14. The acute myeloid leukemia associated AML1-ETO fusion protein alters the transcriptome and cellular progression in a single-oncogene expressing in vitro induced pluripotent stem cell based granulocyte differentiation model

Author

Tijchon, Esther, primary, Yi, Guoqiang, additional, Mandoli, Amit, additional, Smits, Jos G. A., additional, Ferrari, Francesco, additional, Heuts, Branco M. H., additional, Wijnen, Falco, additional, Kim, Bowon, additional, Janssen-Megens, Eva M., additional, Schuringa, Jan Jacob, additional, and Martens, Joost H. A., additional

Published
2019
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15. Dendritic Cells Actively Limit Interleukin-10 Production Under Inflammatory Conditions via DC-SCRIPT and Dual-Specificity Phosphatase 4

Author

Søndergaard, Jonas Nørskov, primary, van Heeringen, Simon J., additional, Looman, Maaike W. G., additional, Tang, Chunling, additional, Triantis, Vassilis, additional, Louche, Pauline, additional, Janssen-Megens, Eva M., additional, Sieuwerts, Anieta M., additional, Martens, John W. M., additional, Logie, Colin, additional, Stunnenberg, Hendrik G., additional, Ansems, Marleen, additional, and Adema, Gosse J., additional

Published
2018
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16. Combined HAT/EZH2 modulation leads to cancer-selective cell death

Author

Petraglia, Francesca, primary, Singh, Abhishek A., additional, Carafa, Vincenzo, additional, Nebbioso, Angela, additional, Conte, Mariarosaria, additional, Scisciola, Lucia, additional, Valente, Sergio, additional, Baldi, Alfonso, additional, Mandoli, Amit, additional, Petrizzi, Valeria Belsito, additional, Ingenito, Concetta, additional, De Falco, Sandro, additional, Cicatiello, Valeria, additional, Apicella, Ivana, additional, Janssen-Megens, Eva M., additional, Kim, Bowon, additional, Yi, Guoqiang, additional, Logie, Colin, additional, Heath, Simon, additional, Ruvo, Menotti, additional, Wierenga, Albertus T.J., additional, Flicek, Paul, additional, Yaspo, Marie Laure, additional, Della Valle, Veronique, additional, Bernard, Olivier, additional, Tomassi, Stefano, additional, Novellino, Ettore, additional, Feoli, Alessandra, additional, Sbardella, Gianluca, additional, Gut, Ivo, additional, Vellenga, Edo, additional, Stunnenberg, Hendrik G., additional, Mai, Antonello, additional, Martens, Joost H.A., additional, and Altucci, Lucia, additional

Published
2018
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17. Multi-omics profiling reveals a distinctive epigenome signature for high-risk acute promyelocytic leukemia

Author

Singh, Abhishek A., primary, Petraglia, Francesca, additional, Nebbioso, Angela, additional, Yi, Guoqiang, additional, Conte, Mariarosaria, additional, Valente, Sergio, additional, Mandoli, Amit, additional, Scisciola, Lucia, additional, Lindeboom, Rik, additional, Kerstens, Hinri, additional, Janssen-Megens, Eva M., additional, Pourfarzad, Farzin, additional, Habibi, Ehsan, additional, Berentsen, Kim, additional, Kim, Bowon, additional, Logie, Colin, additional, Heath, Simon, additional, Wierenga, Albertus T.J., additional, Clarke, Laura, additional, Flicek, Paul, additional, Jansen, Joop H., additional, Kuijpers, Taco, additional, Yaspo, Marie Laure, additional, Valle, Veronique Della, additional, Bernard, Olivier, additional, Gut, Ivo, additional, Vellenga, Edo, additional, Stunnenberg, Hendrik G., additional, Mai, Antonello, additional, Altucci, Lucia, additional, and Martens, Joost H.A., additional

Published
2018
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18. Comparative analysis of neutrophil and monocyte epigenomes

Author

Rico, Daniel, primary, Martens, Joost HA, additional, Downes, Kate, additional, Carrillo-de-Santa-Pau, Enrique, additional, Pancaldi, Vera, additional, Breschi, Alessandra, additional, Richardson, David, additional, Heath, Simon, additional, Saeed, Sadia, additional, Frontini, Mattia, additional, Chen, Lu, additional, Watt, Stephen, additional, Müller, Fabian, additional, Clarke, Laura, additional, Kerstens, Hindrik HD, additional, Wilder, Steven P, additional, Palumbo, Emilio, additional, Djebali, Sarah, additional, Raineri, Emanuele, additional, Merkel, Angelika, additional, Esteve-Codina, Anna, additional, Sultan, Marc, additional, van Bommel, Alena, additional, Gut, Marta, additional, Yaspo, Marie-Laure, additional, Rubio, Miriam, additional, Fernandez, José María, additional, Attwood, Anthony, additional, de la Torre, Victor, additional, Royo, Romina, additional, Fragkogianni, Stamatina, additional, Gelpí, Josep Lluis, additional, Torrents, David, additional, Iotchkova, Valentina, additional, Logie, Colin, additional, Aghajanirefah, Ali, additional, Singh, Abhishek A, additional, Janssen-Megens, Eva M, additional, Berentsen, Kim, additional, Erber, Wendy, additional, Rendon, Augusto, additional, Kostadima, Myrto, additional, Loos, Remco, additional, van der Ent, Martijn A, additional, Kaan, Anita, additional, Sharifi, Nilofar, additional, Paul, Dirk S, additional, Ifrim, Daniela C, additional, Quintin, Jessica, additional, Love, Michael I., additional, Pisano, David G, additional, Burden, Frances, additional, Foad, Nicola, additional, Farrow, Samantha, additional, Zerbino, Daniel R, additional, Dunham, Ian, additional, Kuijpers, Tacow, additional, Lehrach, Hans, additional, Lengauer, Thomas, additional, Bertone, Paul, additional, Netea, Mihai G, additional, Vingron, Martin, additional, Beck, Stephan, additional, Flicek, Paul, additional, Gut, Ivo, additional, Ouwehand, Willem H, additional, Bock, Christoph, additional, Soranzo, Nicole, additional, Guigo, Rodericw, additional, Valencia, Alfonso, additional, and Stunnenberg, Hendrik G, additional

Published
2017
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19. The Hematopoietic Transcription Factors RUNX1 and ERG Prevent AML1-ETO Oncogene Overexpression and Onset of the Apoptosis Program in t(8;21) AMLs

Author

Mandoli, Amit, primary, Singh, Abhishek A., additional, Prange, Koen H.M., additional, Tijchon, Esther, additional, Oerlemans, Marjolein, additional, Dirks, Rene, additional, Ter Huurne, Menno, additional, Wierenga, Albertus T.J., additional, Janssen-Megens, Eva M., additional, Berentsen, Kim, additional, Sharifi, Nilofar, additional, Kim, Bowon, additional, Matarese, Filomena, additional, Nguyen, Luan N., additional, Hubner, Nina C., additional, Rao, Nagesha A., additional, van den Akker, Emile, additional, Altucci, Lucia, additional, Vellenga, Edo, additional, Stunnenberg, Hendrik G., additional, and Martens, Joost H.A., additional

Published
2016
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20. Lineage-Specific Genome Architecture Links Enhancers and Non-coding Disease Variants to Target Gene Promoters

Author

Javierre, Biola M., primary, Burren, Oliver S., additional, Wilder, Steven P., additional, Kreuzhuber, Roman, additional, Hill, Steven M., additional, Sewitz, Sven, additional, Cairns, Jonathan, additional, Wingett, Steven W., additional, Várnai, Csilla, additional, Thiecke, Michiel J., additional, Burden, Frances, additional, Farrow, Samantha, additional, Cutler, Antony J., additional, Rehnström, Karola, additional, Downes, Kate, additional, Grassi, Luigi, additional, Kostadima, Myrto, additional, Freire-Pritchett, Paula, additional, Wang, Fan, additional, Stunnenberg, Hendrik G., additional, Todd, John A., additional, Zerbino, Daniel R., additional, Stegle, Oliver, additional, Ouwehand, Willem H., additional, Frontini, Mattia, additional, Wallace, Chris, additional, Spivakov, Mikhail, additional, Fraser, Peter, additional, Martens, Joost H., additional, Kim, Bowon, additional, Sharifi, Nilofar, additional, Janssen-Megens, Eva M., additional, Yaspo, Marie-Laure, additional, Linser, Matthias, additional, Kovacsovics, Alexander, additional, Clarke, Laura, additional, Richardson, David, additional, Datta, Avik, additional, and Flicek, Paul, additional

Published
2016
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21. Epigenetic programming of monocyte-to-macrophage differentiation and trained innate immunity

Author

Saeed, Sadia Quintin, Jessica Kerstens, Hindrik H. D. Rao, Nagesha A. Aghajanirefah, Ali Matarese, Filomena Cheng, Shih-Chin Ratter, Jacqueline Berentsen, Kim van der Ent, Martijn A. Sharifi, Nilofar Janssen-Megens, Eva M. Ter Huurne, Menno Mandoli, Amit van Schaik, Tom Ng, Aylwin and Burden, Frances Downes, Kate Frontini, Mattia Kumar, Vinod and Giamarellos-Bourboulis, Evangelos J. Ouwehand, Willem H. van der Meer, Jos W. M. Joosten, Leo A. B. Wijmenga, Cisca and Martens, Joost H. A. Xavier, Ramnik J. Logie, Colin Netea, Mihai G. Stunnenberg, Hendrik G.

Abstract

Monocyte differentiation into macrophages represents a cornerstone process for host defense. Concomitantly, immunological imprinting of either tolerance or trained immunity determines the functional fate of macrophages and susceptibility to secondary infections. We characterized the transcriptomes and epigenomes in four primary cell types: monocytes and in vitro-differentiated naive, tolerized, and trained macrophages. Inflammatory and metabolic pathways were modulated in macrophages, including decreased inflammasome activation, and we identified pathways functionally implicated in trained immunity. beta-glucan training elicits an exclusive epigenetic signature, revealing a complex network of enhancers and promoters. Analysis of transcription factor motifs in deoxyribonuclease I hypersensitive sites at cell-type-specific epigenetic loci unveiled differentiation and treatment-specific repertoires. Altogether, we provide a resource to understand the epigenetic changes that underlie innate immunity in humans.

Published
2014

22. Streptococcus pneumoniae Folate Biosynthesis Responds to Environmental CO2 Levels

Author

Burghout, Peter, Zomer, Aldert, van der Gaast-de Jongh, Christa E, Janssen-Megens, Eva M, Françoijs, Kees-Jan, Stunnenberg, Hendrik G, Hermans, Peter W M, LS Klinisch Onderzoek Wagenaar, and LS Klinisch Onderzoek Wagenaar

Subjects
Energy and redox metabolism [NCMLS 4], Mutant, medicine.disease_cause, Microbiology, Gene Knockout Techniques, Folic Acid, Carbonic anhydrase, Insertional, Streptococcus pneumoniae, medicine, Peptide Synthases, Gene, Pathogen, Molecular Biology, Carbonic Anhydrases, biology, Mutagenesis, Folylpolyglutamate synthase, Pathogenesis and modulation of inflammation Infection and autoimmunity [N4i 1], Articles, Carbon Dioxide, Mutagenesis, Insertional, Biochemistry, biology.protein, DNA Transposable Elements, Intracellular
Abstract

Although carbon dioxide (CO 2 ) is known to be essential for Streptococcus pneumoniae growth, it is poorly understood how this respiratory tract pathogen adapts to the large changes in environmental CO 2 levels it encounters during transmission, host colonization, and disease. To identify the molecular mechanisms that facilitate pneumococcal growth under CO 2 -poor conditions, we generated a random S. pneumoniae R6 mariner transposon mutant library representing mutations in 1,538 different genes and exposed it to CO 2 -poor ambient air. With Tn-seq, we found mutations in two genes that were involved in S. pneumoniae adaptation to changes in CO 2 availability. The gene pca , encoding pneumococcal carbonic anhydrase (PCA), was absolutely essential for S. pneumoniae growth under CO 2 -poor conditions. PCA catalyzes the reversible hydration of endogenous CO 2 to bicarbonate (HCO 3 − ) and was previously demonstrated to facilitate HCO 3 − -dependent fatty acid biosynthesis. The gene folC that encodes the dihydrofolate/folylpolyglutamate synthase was required at the initial phase of bacterial growth under CO 2 -poor culture conditions. FolC compensated for the growth-phase-dependent decrease in S. pneumoniae intracellular long-chain ( n > 3) polyglutamyl folate levels, which was most pronounced under CO 2 -poor growth conditions. In conclusion, S. pneumoniae adaptation to changes in CO 2 availability involves the retention of endogenous CO 2 and the preservation of intracellular long-chain polyglutamyl folate pools.

Published
2013

23. Glucocorticoid receptor and nuclear factor kappa-b affect three-dimensional chromatin organization

Author

Kuznetsova, Tatyana, primary, Wang, Shuang-Yin, additional, Rao, Nagesha A., additional, Mandoli, Amit, additional, Martens, Joost H. A., additional, Rother, Nils, additional, Aartse, Aafke, additional, Groh, Laszlo, additional, Janssen-Megens, Eva M., additional, Li, Guoliang, additional, Ruan, Yijun, additional, Logie, Colin, additional, and Stunnenberg, Hendrik G., additional

Published
2015
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24. Streptococcus pneumoniae folate biosynthesis responds to environmental CO2 levels

Author

LS Klinisch Onderzoek Wagenaar, Burghout, Peter, Zomer, Aldert, van der Gaast-de Jongh, Christa E, Janssen-Megens, Eva M, Françoijs, Kees-Jan, Stunnenberg, Hendrik G, Hermans, Peter W M, LS Klinisch Onderzoek Wagenaar, Burghout, Peter, Zomer, Aldert, van der Gaast-de Jongh, Christa E, Janssen-Megens, Eva M, Françoijs, Kees-Jan, Stunnenberg, Hendrik G, and Hermans, Peter W M

Published
2013

25. RAD21 Cooperates with Pluripotency Transcription Factors in the Maintenance of Embryonic Stem Cell Identity

Author

Buchholz, Frank, Nitzsche, Anja, Paszkowski-Rogacz, Maciej, Matarese, Filomena, Janssen-Megens, Eva M., Hubner, Nina C., Schulz, Herbert, de Vries, Ingrid, Ding, Li, Huebner, Norbert, Mann, Matthias, Stunnenberg, Hendrik G., Buchholz, Frank, Nitzsche, Anja, Paszkowski-Rogacz, Maciej, Matarese, Filomena, Janssen-Megens, Eva M., Hubner, Nina C., Schulz, Herbert, de Vries, Ingrid, Ding, Li, Huebner, Norbert, Mann, Matthias, and Stunnenberg, Hendrik G.

Abstract

For self-renewal, embryonic stem cells (ESCs) require the expression of specific transcription factors accompanied by a particular chromosome organization to maintain a balance between pluripotency and the capacity for rapid differentiation. However, how transcriptional regulation is linked to chromosome organization in ESCs is not well understood. Here we show that the cohesin component RAD21 exhibits a functional role in maintaining ESC identity through association with the pluripotency transcriptional network. ChIP-seq analyses of RAD21 reveal an ESC specific cohesin binding pattern that is characterized by CTCF independent co-localization of cohesin with pluripotency related transcription factors Oct4, Nanog, Sox2, Esrrb and Klf4. Upon ESC differentiation, most of these binding sites disappear and instead new CTCF independent RAD21 binding sites emerge, which are enriched for binding sites of transcription factors implicated in early differentiation. Furthermore, knock-down of RAD21 causes expression changes that are similar to expression changes after Nanog depletion, demonstrating the functional relevance of the RAD21 - pluripotency transcriptional network association. Finally, we show that Nanog physically interacts with the cohesin or cohesin interacting proteins STAG1 and WAPL further substantiating this association. Based on these findings we propose that a dynamic placement of cohesin by pluripotency transcription factors contributes to a chromosome organization supporting the ESC expression program.

Published
2011

27. The metagenome of the marine anammox bacterium ‘Candidatus Scalindua profunda’ illustrates the versatility of this globally important nitrogen cycle bacterium

Author

van de Vossenberg, Jack, primary, Woebken, Dagmar, additional, Maalcke, Wouter J., additional, Wessels, Hans J. C. T., additional, Dutilh, Bas E., additional, Kartal, Boran, additional, Janssen‐Megens, Eva M., additional, Roeselers, Guus, additional, Yan, Jia, additional, Speth, Daan, additional, Gloerich, Jolein, additional, Geerts, Wim, additional, van der Biezen, Erwin, additional, Pluk, Wendy, additional, Francoijs, Kees‐Jan, additional, Russ, Lina, additional, Lam, Phyllis, additional, Malfatti, Stefanie A., additional, Tringe, Susannah Green, additional, Haaijer, Suzanne C. M., additional, Op den Camp, Huub J. M., additional, Stunnenberg, Henk G., additional, Amann, Rudi, additional, Kuypers, Marcel M. M., additional, and Jetten, Mike S. M., additional

Published
2012
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28. RAD21 Cooperates with Pluripotency Transcription Factors in the Maintenance of Embryonic Stem Cell Identity

Author

Nitzsche, Anja, primary, Paszkowski-Rogacz, Maciej, additional, Matarese, Filomena, additional, Janssen-Megens, Eva M., additional, Hubner, Nina C., additional, Schulz, Herbert, additional, de Vries, Ingrid, additional, Ding, Li, additional, Huebner, Norbert, additional, Mann, Matthias, additional, Stunnenberg, Hendrik G., additional, and Buchholz, Frank, additional

Published
2011
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30. Streptococcus pneumoniae Folate Biosynthesis Responds to Environmental CO2 Levels.

Author

Burghout, Peter, Zomer, Aldert, van der Gaast-de Jongh, Christa E., Janssen-Megens, Eva M., Françoijs, Kees-Jan, Stunnenberg, Hendrik G., and Hermans, Peter W. M.

Subjects
*CARBON dioxide, *STREPTOCOCCUS pneumoniae, *FATTY acids, *MOBILE genetic elements, *GENES, *BACTERIAL growth
Abstract

Although carbon dioxide (CO2) is known to be essential for Streptococcus pneumoniae growth, it is poorly understood how this respiratory tract pathogen adapts to the large changes in environmental CO2 levels it encounters during transmission, host colonization, and disease. To identify the molecular mechanisms that facilitate pneumococcal growth under CO2-poor conditions, we generated a random S. pneumoniae R6 mariner transposon mutant library representing mutations in 1,538 different genes and exposed it to CO2-poor ambient air. With Tn-seq, we found mutations in two genes that were involved in S. pneumoniae adaptation to changes in CO2 availability. The gene pea, encoding pneumococcal carbonic anhydrase (PCA), was absolutely essential for S. pneumoniae growth under CO2-poor conditions. PCA catalyzes the reversible hydration of endogenous CO2 to bicarbonate (HCO3-) and was previously demonstrated to facilitate HCO3--dependent fatty acid biosynthesis. The gene folC that encodes the dihydrofolate/folylpolyglutamate synthase was required at the initial phase of bacterial growth under CO2-poor culture conditions. FolC compensated for the growth-phase-dependent decrease in S. pneumoniae intracellular long-chain (n > 3) polyglutamyl folate levels, which was most pronounced under CO2-poor growth conditions. In conclusion, S. pneumoniae adaptation to changes in CO2 availability involves the retention of endogenous CO2 and the preservation of intracellular long-chain polyglutamyl folate pools. [ABSTRACT FROM AUTHOR]

Published
2013
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31. Combined HAT/EZH2 modulation leads to cancer-selective cell death

Author

Valeria Cicatiello, Alfonso Baldi, Eva M. Janssen-Megens, Simon Heath, Olivier A. Bernard, Mariarosaria Conte, Edo Vellenga, Gianluca Sbardella, Alessandra Feoli, Antonello Mai, Francesca Petraglia, Concetta Ingenito, Bowon Kim, Valeria Belsito Petrizzi, Guoqiang Yi, Stefano Tomassi, Abhishek Singh, Angela Nebbioso, Ivo Gut, Paul Flicek, Albertus T. J. Wierenga, Marie-Laure Yaspo, Joost H.A. Martens, Hendrik G. Stunnenberg, Ivana Apicella, Lucia Scisciola, Sergio Valente, Ettore Novellino, Véronique Della Valle, Menotti Ruvo, Sandro De Falco, Amit Mandoli, Colin Logie, Vincenzo Carafa, Lucia Altucci, Università degli studi della Campania 'Luigi Vanvitelli', Radboud university [Nijmegen], Institut de Recherche Vétérinaire de Tunisie (IRVT), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Ospedale Umberto I, Istituto di Biofisica e Genetica 'Adriano Buzzati Traverso', Consiglio Nazionale delle Ricerche (CNR), Centro Nacional de Analisis Genomico [Barcelona] (CNAG), CNR – Istituto di Biostrutture e Bioimmagini, University Medical Center Groningen [Groningen] (UMCG), European Bioinformatics Institute [Hinxton] (EMBL-EBI), EMBL Heidelberg, Max Planck Institute for Molecular Genetics (MPIMG), Max-Planck-Gesellschaft, Hématopoïèse normale et pathologique (U1170 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR), Department of Medicinal Chemistry and Technologies, Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Università degli studi di Napoli Federico II, Università degli Studi di Salerno (UNISA), Centro Nacional de Análisi Genómico (CNAG), Centro Nacional de Análisis Genómico, This work was supported by BLUEPRINT (282510), Programma VALERE: Vanvitelli per la Ricerca, the Italian-Flag Project-EPIGEN, PRIN-20152TE5PK, the Italian association against cancer (AIRC-17217), the Dutch Cancer Foundation (KWF kun 2011–4937) and Netherlands organization for Scientific Research (NWO-VIDI)., Petraglia, Francesca, Singh, Abhishek A., Carafa, Vincenzo, Nebbioso, Angela, Conte, Mariarosaria, Scisciola, Lucia, Valente, Sergio, Baldi, Alfonso, Mandoli, Amit, Petrizzi, Valeria Belsito, Ingenito, Concetta, De Falco, Sandro, Cicatiello, Valeria, Apicella, Ivana, Janssen-Megens, Eva M., Kim, Bowon, Yi, Guoqiang, Logie, Colin, Heath, Simon, Ruvo, Menotti, Wierenga, Albertus T. J., Flicek, Paul, Yaspo, Marie Laure, Della Valle, Veronique, Bernard, Olivier, Tomassi, Stefano, Novellino, Ettore, Feoli, Alessandra, Sbardella, Gianluca, Gut, Ivo, Vellenga, Edo, Stunnenberg, Hendrik G., Mai, Antonello, Martens, Joost H. A., Altucci, Lucia, Guided Treatment in Optimal Selected Cancer Patients (GUTS), and Stem Cell Aging Leukemia and Lymphoma (SALL)

Subjects
0301 basic medicine, acetylation, apoptosis, cancer, epigenetics, methylation, oncology, Programmed cell death, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, In vivo, medicine, Molecular Biology, business.industry, Cancer, Epigenetics, Apoptosis, Acetylation, Methylation, EZH2, Apoptosi, Epigenetic, Epigenome, medicine.disease, 3. Good health, Leukemia, 030104 developmental biology, Oncology, Cancer research, business, Ex vivo, Research Paper
Abstract

Contains fulltext : 197351.pdf (Publisher’s version ) (Open Access) Epigenetic alterations have been associated with both pathogenesis and progression of cancer. By screening of library compounds, we identified a novel hybrid epi-drug MC2884, a HAT/EZH2 inhibitor, able to induce bona fide cancer-selective cell death in both solid and hematological cancers in vitro, ex vivo and in vivo xenograft models. Anticancer action was due to an epigenome modulation by H3K27me3, H3K27ac, H3K9/14ac decrease, and to caspase-dependent apoptosis induction. MC2884 triggered mitochondrial pathway apoptosis by up-regulation of cleaved-BID, and strong down-regulation of BCL2. Even aggressive models of cancer, such as p53(-/-) or TET2(-/-) cells, responded to MC2884, suggesting MC2884 therapeutic potential also for the therapy of TP53 or TET2-deficient human cancers. MC2884 induced massive apoptosis in ex vivo human primary leukemia blasts with poor prognosis in vivo, by targeting BCL2 expression. MC2884-treatment reduced acetylation of the BCL2 promoter at higher level than combined p300 and EZH2 inhibition. This suggests a key role for BCL-2 reduction in potentiating responsiveness, also in combination therapy with BCL2 inhibitors. Finally, we identified both the mechanism of MC2884 action as well as a potential therapeutic scheme of its use. Altogether, this provides proof of concept for the use of epi-drugs coupled with epigenome analyses to 'personalize' precision medicine.

Published
2018
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32. The Hematopoietic Transcription Factors RUNX1 and ERG Prevent AML1-ETO Oncogene Overexpression and Onset of the Apoptosis Program in t(8;21) AMLs

Author

René A.M. Dirks, Abhishek Singh, Koen H.M. Prange, Esther Tijchon, Filomena Matarese, Luan Nguyen, Kim Berentsen, Edo Vellenga, Lucia Altucci, Bowon Kim, Menno ter Huurne, Eva M. Janssen-Megens, Marjolein M. P. Oerlemans, Hendrik G. Stunnenberg, Nina C. Hubner, Amit Mandoli, Emile van den Akker, Nagesha A.S. Rao, Nilofar Sharifi, Albertus T. J. Wierenga, Joost H.A. Martens, Mandoli, Amit, Singh, Abhishek A, Prange, Koen H. M, Tijchon, Esther, Oerlemans, Marjolein, Dirks, Rene, Ter Huurne, Menno, Wierenga, Albertus T. J, Janssen Megens, Eva M, Berentsen, Kim, Sharifi, Nilofar, Kim, Bowon, Matarese, Filomena, Nguyen, Luan N, Hubner, Nina C, Rao, Nagesha A, van den Akker, Emile, Altucci, Lucia, Vellenga, Edo, Stunnenberg, Hendrik G, Martens, Joost H. A., Guided Treatment in Optimal Selected Cancer Patients (GUTS), Stem Cell Aging Leukemia and Lymphoma (SALL), and Medical Biochemistry

Subjects
0301 basic medicine, Oncogene Proteins, Fusion, Chromosomes, Human, Pair 21, epigenome, DEFINITIVE HEMATOPOIESIS, RUNX1 and ERG, Translocation, Genetic, chemistry.chemical_compound, RUNX1 Translocation Partner 1 Protein, hemic and lymphatic diseases, AML1-ETO, Promoter Regions, Genetic, Induced pluripotent stem cell, GENE-EXPRESSION, HDAC INHIBITION, iPSC, GRANULOCYTIC DIFFERENTIATION, apoptosis, Myeloid leukemia, Acetylation, Leukemia, Myeloid, Acute, Haematopoiesis, RUNX1, Gene Knockdown Techniques, FLI1, Core Binding Factor Alpha 2 Subunit, PLURIPOTENT STEM-CELLS, Chromosomes, Human, Pair 8, Protein Binding, Cell Survival, ACUTE MYELOID-LEUKEMIA, Biology, acute myeloid leukemia, Histone Deacetylases, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Transcriptional Regulator ERG, Cell Line, Tumor, Humans, Cell Lineage, HISTONE H4, Molecular Biology, AML1/ETO, neoplasms, Transcription factor, Base Sequence, Genome, Human, GENOME-WIDE, Oncogenes, Epigenome, apoptosi, Hematopoiesis, SELF-RENEWAL, 030104 developmental biology, chemistry, Cancer research, TAL1
Abstract

Contains fulltext : 163345.pdf (Publisher’s version ) (Open Access) The t(8;21) acute myeloid leukemia (AML)-associated oncoprotein AML1-ETO disrupts normal hematopoietic differentiation. Here, we have investigated its effects on the transcriptome and epigenome in t(8,21) patient cells. AML1-ETO binding was found at promoter regions of active genes with high levels of histone acetylation but also at distal elements characterized by low acetylation levels and binding of the hematopoietic transcription factors LYL1 and LMO2. In contrast, ERG, FLI1, TAL1, and RUNX1 bind at all AML1-ETO-occupied regulatory regions, including those of the AML1-ETO gene itself, suggesting their involvement in regulating AML1-ETO expression levels. While expression of AML1-ETO in myeloid differentiated induced pluripotent stem cells (iPSCs) induces leukemic characteristics, overexpression increases cell death. We find that expression of wild-type transcription factors RUNX1 and ERG in AML is required to prevent this oncogene overexpression. Together our results show that the interplay of the epigenome and transcription factors prevents apoptosis in t(8;21) AML cells.

Published
2016
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