The KDM5 family is required for activation of pro-proliferative cell cycle genes during adipocyte differentiation
| Autor: | Ronni Nielsen, Qin Yan, Søren Fisker Schmidt, Jesper Grud Skat Madsen, Ann-Sofie B. Brier, Anne Loft, Susanne Mandrup, Zongzhi Liu, Hinrich Gronemeyer, Thomas Rosengren |
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| Přispěvatelé: | University of Southern Denmark (SDU), University of Copenhagen = Københavns Universitet (UCPH), Yale School of Medicine [New Haven, Connecticut] (YSM), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), univOAK, Archive ouverte |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Gene Expression Regulation Histones/metabolism Histone Demethylases/*genetics/metabolism Biology Models Biological Cell Line Promoter Regions Histones Mice 03 medical and health sciences Genetic Models Demethylase activity Gene expression Journal Article Cell Differentiation/*genetics [SDV.BBM] Life Sciences [q-bio]/Biochemistry Molecular Biology Adipocytes Genetics Animals [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Promoter Regions Genetic Cell Cycle/*genetics Cell Proliferation Histone Demethylases Regulation of gene expression Gene knockdown Adipogenesis Gene regulation Chromatin and Epigenetics Cell Cycle Cell Differentiation Adipocytes/*cytology/*metabolism Cell cycle Biological Cell Cycle Gene Cell biology Enzyme Activation 030104 developmental biology Multigene Family KDM5A biology.protein H3K4me3 Adipogenesis/genetics Protein Binding |
| Zdroj: | Brier, A-S B, Loft, A, Madsen, J G S, Nielsen, T R, Nielsen, R, Schmidt, S F, Liu, Z, Yan, Q, Gronemeyer, H & Mandrup, S 2017, ' The KDM 5 family is required for activation of pro-proliferative cell cycle genes during adipocyte differentiation ', Nucleic Acids Research, vol. 45, no. 4, pp. 1743-1759 . https://doi.org/10.1093/nar/gkw1156 Nucleic Acids Research Nucleic Acids Research, 2017, 45 (4), pp.1743-1759. ⟨10.1093/nar/gkw1156⟩ Brier, A-S B, Loft, A, Madsen, J G S, Rosengren, T, Nielsen, R, Schmidt, S F, Liu, Z, Yan, Q, Gronemeyer, H & Mandrup, S 2017, ' The KDM5 family is required for activation of pro-proliferative cell cycle genes during adipocyte differentiation ', Nucleic Acids Research, vol. 45, no. 4, pp. 1743-1759 . https://doi.org/10.1093/nar/gkw1156 |
| ISSN: | 1362-4962 0305-1048 |
| DOI: | 10.1093/nar/gkw1156 |
| Popis: | The KDM5 family of histone demethylases removes the H3K4 tri-methylation (H3K4me3) mark frequently found at promoter regions of actively transcribed genes and is therefore generally considered to contribute to corepression. In this study, we show that knockdown (KD) of all expressed members of the KDM5 family in white and brown preadipocytes leads to deregulated gene expression and blocks differentiation to mature adipocytes. KDM5 KD leads to a considerable increase in H3K4me3 at promoter regions; however, these changes in H3K4me3 have a limited effect on gene expression per se. By contrast, genome-wide analyses demonstrate that KDM5A is strongly enriched at KDM5-activated promoters, which generally have high levels of H3K4me3 and are associated with highly expressed genes. We show that KDM5-activated genes include a large set of cell cycle regulators and that the KDM5s are necessary for mitotic clonal expansion in 3T3-L1 cells, indicating that KDM5 KD may interfere with differentiation in part by impairing proliferation. Notably, the demethylase activity of KDM5A is required for activation of at least a subset of pro-proliferative cell cycle genes. In conclusion, the KDM5 family acts as dual modulators of gene expression in preadipocytes and is required for early stage differentiation and activation of pro-proliferative cell cycle genes. |
| Databáze: | OpenAIRE |
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