Please use this identifier to cite or link to this item: https://doi.org/10.1093/nar/gkw483
Title: G9a promotes proliferation and inhibits cell cycle exit during myogenic differentiation
Authors: Rao, Vinay Kumar|
Ow, Jin Rong
SHILPA RANI SHANKAR 
Narendra Bharathy
MANIKANDAN JAYAPAL 
WANG YAJU 
RESHMA TANEJA 
Keywords: Animals
Cell Line
Cell Proliferation
E2F1 Transcription Factor
Gene Expression Regulation
Gene Knockdown Techniques
Histone-Lysine N-Methyltransferase
Histones
Lysine
Methylation
Mice, Inbred C57BL
MyoD Protein
Myoblasts
Promoter Regions, Genetic
p300-CBP Transcription Factors
Cell Cycle
Cell Differentiation
Muscle Development
Issue Date: 30-Sep-2016
Publisher: Oxford University Press
Citation: Rao, Vinay Kumar|, Ow, Jin Rong, SHILPA RANI SHANKAR, Narendra Bharathy, MANIKANDAN JAYAPAL, WANG YAJU, RESHMA TANEJA (2016-09-30). G9a promotes proliferation and inhibits cell cycle exit during myogenic differentiation. Nucleic Acids Research 44 (17) : 8129-8143. ScholarBank@NUS Repository. https://doi.org/10.1093/nar/gkw483
Rights: Attribution 4.0 International
Abstract: Differentiation of skeletal muscle cells, like most other cell types, requires a permanent exit from the cell cycle. The epigenetic programming underlying these distinct cellular states is not fully understood. In this study, we provide evidence that the lysine methyltransferase G9a functions as a central axis to regulate proliferation and differentiation of skeletal muscle cells. Transcriptome analysis of G9a knockdown cells revealed deregulation of many cell cycle regulatory genes. We demonstrate that G9a enhances cellular proliferation by two distinct mechanisms. G9a blocks cell cycle exit via methylation-dependent transcriptional repression of the MyoD target genes p21(Cip/Waf1) and Rb1. In addition, it activates E2F1-target genes in a methyltransferase activity-independent manner. We show that G9a is present in the E2F1/PCAF complex, and enhances PCAF occupancy and histone acetylation marks at E2F1-target promoters. Interestingly, G9a preferentially associates with E2F1 at the G1/S phase and with MyoD at the G2/M phase. Our results provide evidence that G9a functions both as a co-activator and a co-repressor to enhance cellular proliferation and inhibit myogenic differentiation.
Source Title: Nucleic Acids Research
URI: http://scholarbank.nus.edu.sg/handle/10635/137841
ISSN: 03051048
DOI: 10.1093/nar/gkw483
Rights: Attribution 4.0 International
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