PMID- 27899593
OWN - NLM
STAT- MEDLINE
DCOM- 20171002
LR  - 20231104
IS  - 1362-4962 (Electronic)
IS  - 0305-1048 (Print)
IS  - 0305-1048 (Linking)
VI  - 45
IP  - 4
DP  - 2017 Feb 28
TI  - The KDM5 family is required for activation of pro-proliferative cell cycle genes 
      during adipocyte differentiation.
PG  - 1743-1759
LID - 10.1093/nar/gkw1156 [doi]
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.
CI  - (c) The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic 
      Acids Research.
FAU - Brier, Ann-Sofie B
AU  - Brier AB
AD  - Department of Biochemistry and Molecular Biology, University of Southern Denmark, 
      5230 Odense M, Denmark.
FAU - Loft, Anne
AU  - Loft A
AD  - Department of Biochemistry and Molecular Biology, University of Southern Denmark, 
      5230 Odense M, Denmark.
FAU - Madsen, Jesper G S
AU  - Madsen JGS
AD  - Department of Biochemistry and Molecular Biology, University of Southern Denmark, 
      5230 Odense M, Denmark.
AD  - The Novo Nordisk Foundation Center for Basic Metabolic Research, University of 
      Copenhagen, 2200 Copenhagen N, Denmark.
FAU - Rosengren, Thomas
AU  - Rosengren T
AD  - Department of Biochemistry and Molecular Biology, University of Southern Denmark, 
      5230 Odense M, Denmark.
FAU - Nielsen, Ronni
AU  - Nielsen R
AD  - Department of Biochemistry and Molecular Biology, University of Southern Denmark, 
      5230 Odense M, Denmark.
FAU - Schmidt, Soren F
AU  - Schmidt SF
AD  - Department of Biochemistry and Molecular Biology, University of Southern Denmark, 
      5230 Odense M, Denmark.
FAU - Liu, Zongzhi
AU  - Liu Z
AD  - Department of Pathology, Yale School of Medicine, New Haven, CT, USA.
FAU - Yan, Qin
AU  - Yan Q
AD  - Department of Pathology, Yale School of Medicine, New Haven, CT, USA.
FAU - Gronemeyer, Hinrich
AU  - Gronemeyer H
AD  - Equipe Labellisee Ligue Contre le Cancer, Department of Functional Genomics and 
      Cancer, Institut de Genetique et de Biologie Moleculaire et Cellulaire, Centre 
      National de la Recherche Scientifique, UMR7104, Institut National de la Sante et 
      de la Recherche Medicale, U964, Universite de Strasbourg, Illkirch, France.
FAU - Mandrup, Susanne
AU  - Mandrup S
AD  - Department of Biochemistry and Molecular Biology, University of Southern Denmark, 
      5230 Odense M, Denmark.
LA  - eng
GR  - R01 CA076120/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Nucleic Acids Res
JT  - Nucleic acids research
JID - 0411011
RN  - 0 (Histones)
RN  - EC 1.14.11.- (Histone Demethylases)
SB  - IM
MH  - Adipocytes/*cytology/*metabolism
MH  - Adipogenesis/genetics
MH  - Animals
MH  - Cell Cycle/*genetics
MH  - Cell Differentiation/*genetics
MH  - Cell Line
MH  - Cell Proliferation
MH  - Enzyme Activation
MH  - *Gene Expression Regulation
MH  - Histone Demethylases/*genetics/metabolism
MH  - Histones/metabolism
MH  - Mice
MH  - Models, Biological
MH  - *Multigene Family
MH  - Promoter Regions, Genetic
MH  - Protein Binding
PMC - PMC5389521
EDAT- 2016/12/03 06:00
MHDA- 2017/10/03 06:00
PMCR- 2016/11/28
CRDT- 2016/12/01 06:00
PHST- 2016/01/22 00:00 [received]
PHST- 2016/11/05 00:00 [accepted]
PHST- 2016/12/03 06:00 [pubmed]
PHST- 2017/10/03 06:00 [medline]
PHST- 2016/12/01 06:00 [entrez]
PHST- 2016/11/28 00:00 [pmc-release]
AID - gkw1156 [pii]
AID - 10.1093/nar/gkw1156 [doi]
PST - ppublish
SO  - Nucleic Acids Res. 2017 Feb 28;45(4):1743-1759. doi: 10.1093/nar/gkw1156.