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

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1739-1751
Number of pages13
JournalEMBO Journal
Volume31
Issue number7
DOIs
Publication statusPublished - Apr 4 2012
Externally publishedYes

Keywords

  • Epigenetics
  • miR-546
  • Mybbp1a
  • MyoD
  • myogenesis

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)

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  • Cite this

    Yang, C. C., Liu, H., Chen, S. L., Wang, T. H., Hsieh, C. L., Huang, Y., Chen, S. J., Chen, H. C., Yung, B. Y. M., & Tan, B. C. M. (2012). Epigenetic silencing of myogenic gene program by Myb-binding protein 1a suppresses myogenesis. EMBO Journal, 31(7), 1739-1751. https://doi.org/10.1038/emboj.2012.24