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

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

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.

In: Nucleic Acids Research, Vol. 45, No. 4, 28.02.2017, p. 1743-1759.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Brier, A-SB, Loft, A, Madsen, JGS, Rosengren, T, Nielsen, R, Schmidt, SF, 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

APA

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, 45(4), 1743-1759. https://doi.org/10.1093/nar/gkw1156

Vancouver

Brier A-SB, Loft A, Madsen JGS, Rosengren T, Nielsen R, Schmidt SF et al. The KDM5 family is required for activation of pro-proliferative cell cycle genes during adipocyte differentiation. Nucleic Acids Research. 2017 Feb 28;45(4):1743-1759. https://doi.org/10.1093/nar/gkw1156

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. / The KDM5 family is required for activation of pro-proliferative cell cycle genes during adipocyte differentiation. In: Nucleic Acids Research. 2017 ; Vol. 45, No. 4. pp. 1743-1759.

Bibtex

@article{8c2f57e0e77c4211bd2dab18865847bb,
title = "The KDM5 family is required for activation of pro-proliferative cell cycle genes during adipocyte differentiation",
abstract = "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.",
keywords = "Journal Article",
author = "Brier, {Ann-Sofie B} and Anne Loft and Madsen, {Jesper G S} and Thomas Rosengren and Ronni Nielsen and Schmidt, {S{\o}ren F} and Zongzhi Liu and Qin Yan and Hinrich Gronemeyer and Susanne Mandrup",
note = "{\textcopyright} The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.",
year = "2017",
month = feb,
day = "28",
doi = "10.1093/nar/gkw1156",
language = "English",
volume = "45",
pages = "1743--1759",
journal = "Nucleic Acids Research",
issn = "0305-1048",
publisher = "Oxford University Press",
number = "4",

}

RIS

TY - JOUR

T1 - The KDM5 family is required for activation of pro-proliferative cell cycle genes during adipocyte differentiation

AU - Brier, Ann-Sofie B

AU - Loft, Anne

AU - Madsen, Jesper G S

AU - Rosengren, Thomas

AU - Nielsen, Ronni

AU - Schmidt, Søren F

AU - Liu, Zongzhi

AU - Yan, Qin

AU - Gronemeyer, Hinrich

AU - Mandrup, Susanne

N1 - © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

PY - 2017/2/28

Y1 - 2017/2/28

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1093/nar/gkw1156

DO - 10.1093/nar/gkw1156

M3 - Journal article

C2 - 27899593

VL - 45

SP - 1743

EP - 1759

JO - Nucleic Acids Research

JF - Nucleic Acids Research

SN - 0305-1048

IS - 4

ER -

ID: 183008344