Please use this identifier to cite or link to this item: https://doi.org/10.1093/nar/gkw483
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dc.titleG9a promotes proliferation and inhibits cell cycle exit during myogenic differentiation
dc.contributor.authorRao, Vinay Kumar|
dc.contributor.authorOw, Jin Rong
dc.contributor.authorSHILPA RANI SHANKAR
dc.contributor.authorNarendra Bharathy
dc.contributor.authorMANIKANDAN JAYAPAL
dc.contributor.authorWANG YAJU
dc.contributor.authorRESHMA TANEJA
dc.date.accessioned2017-12-11T09:32:42Z
dc.date.available2017-12-11T09:32:42Z
dc.date.issued2016-09-30
dc.identifier.citationRao, 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
dc.identifier.issn03051048
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/137841
dc.description.abstractDifferentiation 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.
dc.language.isoen
dc.publisherOxford University Press
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectAnimals
dc.subjectCell Line
dc.subjectCell Proliferation
dc.subjectE2F1 Transcription Factor
dc.subjectGene Expression Regulation
dc.subjectGene Knockdown Techniques
dc.subjectHistone-Lysine N-Methyltransferase
dc.subjectHistones
dc.subjectLysine
dc.subjectMethylation
dc.subjectMice, Inbred C57BL
dc.subjectMyoD Protein
dc.subjectMyoblasts
dc.subjectPromoter Regions, Genetic
dc.subjectp300-CBP Transcription Factors
dc.subjectCell Cycle
dc.subjectCell Differentiation
dc.subjectMuscle Development
dc.typeArticle
dc.contributor.departmentDEPT OF PHYSIOLOGY
dc.description.doi10.1093/nar/gkw483
dc.description.sourcetitleNucleic Acids Research
dc.description.volume44
dc.description.issue17
dc.description.page8129-8143
dc.identifier.isiut000386158800015
dc.published.statePublished
dc.grant.idNMRC/CBRG/0063/2014
dc.grant.fundingagencyNational Medical Research Council
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