Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/32902
Title: Epigenetic silencing of myogenic gene program by Myb-binding protein 1a suppresses myogenesis
Authors: Yang, CC
Liu, H
Chen, SL
Wang, TH
Hsieh, CL
Huang, Y
Chen, SJ
Chen, HC
Yung, BYM 
Tan, BCM
Keywords: Epigenetics
MiR-546
Mybbp1a
MyoD
Myogenesis
Issue Date: 2012
Source: EMBO Journal, 2012, v. 31, no. 7, p. 1739-1751 How to cite?
Journal: EMBO Journal 
Abstract: 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.
URI: http://hdl.handle.net/10397/32902
ISSN: 0261-4189
DOI: 10.1038/emboj.2012.24
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