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The KDM5 family is required for activation of pro-proliferative cell cycle genes during adipocyte differentiation

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 K...

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Autores principales: Brier, Ann-Sofie B., Loft, Anne, Madsen, Jesper G. S., Rosengren, Thomas, Nielsen, Ronni, Schmidt, Søren F., Liu, Zongzhi, Yan, Qin, Gronemeyer, Hinrich, Mandrup, Susanne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5389521/
https://www.ncbi.nlm.nih.gov/pubmed/27899593
http://dx.doi.org/10.1093/nar/gkw1156
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author Brier, Ann-Sofie B.
Loft, Anne
Madsen, Jesper G. S.
Rosengren, Thomas
Nielsen, Ronni
Schmidt, Søren F.
Liu, Zongzhi
Yan, Qin
Gronemeyer, Hinrich
Mandrup, Susanne
author_facet Brier, Ann-Sofie B.
Loft, Anne
Madsen, Jesper G. S.
Rosengren, Thomas
Nielsen, Ronni
Schmidt, Søren F.
Liu, Zongzhi
Yan, Qin
Gronemeyer, Hinrich
Mandrup, Susanne
author_sort Brier, Ann-Sofie B.
collection PubMed
description 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.
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spelling pubmed-53895212017-04-24 The KDM5 family is required for activation of pro-proliferative cell cycle genes during adipocyte differentiation Brier, Ann-Sofie B. Loft, Anne Madsen, Jesper G. S. Rosengren, Thomas Nielsen, Ronni Schmidt, Søren F. Liu, Zongzhi Yan, Qin Gronemeyer, Hinrich Mandrup, Susanne Nucleic Acids Res Gene regulation, Chromatin and Epigenetics 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. Oxford University Press 2017-02-28 2016-11-28 /pmc/articles/PMC5389521/ /pubmed/27899593 http://dx.doi.org/10.1093/nar/gkw1156 Text en © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Gene regulation, Chromatin and Epigenetics
Brier, Ann-Sofie B.
Loft, Anne
Madsen, Jesper G. S.
Rosengren, Thomas
Nielsen, Ronni
Schmidt, Søren F.
Liu, Zongzhi
Yan, Qin
Gronemeyer, Hinrich
Mandrup, Susanne
The KDM5 family is required for activation of pro-proliferative cell cycle genes during adipocyte differentiation
title The KDM5 family is required for activation of pro-proliferative cell cycle genes during adipocyte differentiation
title_full The KDM5 family is required for activation of pro-proliferative cell cycle genes during adipocyte differentiation
title_fullStr The KDM5 family is required for activation of pro-proliferative cell cycle genes during adipocyte differentiation
title_full_unstemmed The KDM5 family is required for activation of pro-proliferative cell cycle genes during adipocyte differentiation
title_short The KDM5 family is required for activation of pro-proliferative cell cycle genes during adipocyte differentiation
title_sort kdm5 family is required for activation of pro-proliferative cell cycle genes during adipocyte differentiation
topic Gene regulation, Chromatin and Epigenetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5389521/
https://www.ncbi.nlm.nih.gov/pubmed/27899593
http://dx.doi.org/10.1093/nar/gkw1156
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