Epigenetic silencing of myogenic gene program by Myb-binding protein 1a suppresses myogenesis

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题名:	Epigenetic silencing of myogenic gene program by Myb-binding protein 1a suppresses myogenesis
作者:	陳盛良;Yang, Chang-Ching;Liu, Hsuan;Chen, Shen Liang;Wang, Tzu-Hao;Hsieh, Chia-Ling;Huang, Yi;Chen, Shu-Jen;Chen, Hua-Chien;Yung, Benjamin Yat-Ming;Chin-Ming Tan, Bertrand
贡献者:	生醫理工學院生命科學系
关键词:	Animals;Carrier Proteins - genetics;Carrier Proteins - metabolism;Cells, Cultured;Chromatin;Down-Regulation;EMBO07;EMBO09;Epigenetics;Gene Expression;Gene Silencing;Humans;Mice;MicroRNAs - metabolism;miR-546;Mode of action;Molecular biology;Muscle Development - genetics;Muscle, Skeletal - metabolism;Muscular system;Mybbp1a;MyoD;MyoD Protein - genetics;MyoD Protein - metabolism;myogenesis;Nuclear Proteins - genetics;Nuclear Proteins - metabolism;Promoter Regions, Genetic;Proteins
日期:	2012-04-04
上传时间:	2026-04-23 11:12:35 (UTC+8)
出版者:	Wiley-Blackwell;Chichester, UK: John Wiley & Sons, Ltd
摘要:	摘要： Skeletal myogenesis involves highly coordinated steps that integrate developmental cues at the chromatin of muscle progenitors. Here, we identify Myb‐binding protein 1a (Mybbp1a) as a novel negative regulator of muscle‐specific gene expression and myoblast differentiation. The mode of action of Mybbp1a was linked to promoter regulation as illustrated by its interaction with MyoD at the genomic regions of silent muscle‐specific genes as well as its negative effect on MyoD‐mediated transcriptional activity. We propose that Mybbp1a exerts its repressive role by inducing a less permissible chromatin structure following recruitment of negative epigenetic modifiers such as HDAC1/2 and Suv39h1. At the onset of differentiation, Mybbp1a undergoes a promoter disengagement that may be due to the differentiation‐responsive, miR‐546‐mediated downregulation of Mybbp1a expression. Moreover, such alteration gave rise to promoter enrichment of activators and histone acetylation, an epigenetic status amenable to gene activation. Together, these findings unveil a hitherto unrecognized transcriptional co‐repressor role of Mybbp1a in proliferating muscle progenitor cells, and highlight an epigenetic mechanism by which Mybbp1a and miR‐546 interplay to control myoblast differentiation transition. Mybbp1a, a novel co‐repressor of myoblasts differentiation, interacts with MyoD and the repressive chromatin modifiers HDAC1/2 and Suv39h1 at muscle‐specific gene promoters. In response to differentiation cues miR‐546 downregulates Mybbp1a, resulting in histone acetylation and accumulation of transcriptional activators at promoters. 其他題名： EMBO J 出版者： Chichester, UK: John Wiley & Sons, Ltd 出版日期： 2012-04-04 出處： The EMBO journal, 2012-04, Vol.31 (7), p.1739-1751 資源來源： Wiley Online Library 版權： European Molecular Biology Organization 2012 版權： Copyright © 2012 European Molecular Biology Organization 版權： Copyright Nature Publishing Group Apr 4, 2012 版權： Copyright © 2012, European Molecular Biology Organization 2012 European Molecular Biology Organization 識別號： ISSN: 0261-4189 識別號： ISSN: 1460-2075 識別號： EISSN: 1460-2075 識別號： DOI: 10.1038/emboj.2012.24 識別號： PMID: 22333916 識別號： CODEN: EMJODG
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