title: Epigenetic silencing of myogenic gene program by Myb-binding protein 1a suppresses myogenesis.
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.
authors.affiliation: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Kwei-San, Tao-Yuan, Taiwan, ROC.
authors.forename: Chang-Ching
authors.initials: CC
authors.lastname: Yang
authors.forename: Hsuan
authors.initials: H
authors.lastname: Liu
authors.forename: Shen Liang
authors.initials: SL
authors.lastname: Chen
authors.forename: Tzu-Hao
authors.initials: TH
authors.lastname: Wang
authors.forename: Chia-Ling
authors.initials: CL
authors.lastname: Hsieh
authors.forename: Yi
authors.initials: Y
authors.lastname: Huang
authors.forename: Shu-Jen
authors.initials: SJ
authors.lastname: Chen
authors.forename: Hua-Chien
authors.initials: HC
authors.lastname: Chen
authors.forename: Benjamin Yat-Ming
authors.initials: BY
authors.lastname: Yung
authors.forename: Bertrand
authors.initials: B
authors.lastname: Chin-Ming Tan
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins; D015536:Down-Regulation; D015870:Gene Expression; D020868:Gene Silencing; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism; D024510:Muscle Development / Q000235:genetics*; D018482:Muscle, Skeletal / Q000378:metabolism; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D016601:RNA-Binding Proteins; D014157:Transcription Factors
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C572506:MIRN546 microRNA, mouse; D035683:MicroRNAs; C110421:Mybbp1a protein, mouse; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D014157:Transcription Factors