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

Chang Ching Yang, Hsuan Liu, Shen Liang Chen, Tzu Hao Wang, Chia Ling Hsieh, Yi Huang, Shu Jen Chen, Hua Chien Chen, Benjamin Yat Ming Yung, Bertrand Chin Ming Tan

研究成果: 雜誌貢獻期刊論文同行評審

16 引文 斯高帕斯(Scopus)


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.

頁(從 - 到)1739-1751
期刊EMBO Journal
出版狀態已出版 - 4 4月 2012


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