Regulation of skeletal myogenesis by association of the MEF2 transcription factor with class II histone deacetylases

Jianrong Lu, Timothy A. McKinsey, Chun Li Zhang, Eric N. Olson

Research output: Contribution to journalArticle

401 Scopus citations

Abstract

Skeletal muscle differentiation is controlled by associations between myogenic basic-helix-loop-helix and MEF2 transcription factors. We show that chromatin associated with muscle genes regulated by these transcription factors becomes acetylated during myogenesis and that class II histone deacetylases (HDACs), which interact with MEF2, specifically suppress myoblast differentiation. These HDACs do not interact directly with MyoD, yet they suppress its myogenic activity through association with MEF2. Elevating the level of MyoD can override the repression imposed by HDACs on muscle genes. HDAC-mediated repression of myogenesis also can be overcome by CaM kinase and insulin-like growth factor (IGF) signaling. These findings reveal central roles for HDACs in chromatin remodeling during myogenesis and as intranuclear targets for signaling pathways controlled by IGF and CaM kinase.

Original languageEnglish (US)
Pages (from-to)233-244
Number of pages12
JournalMolecular cell
Volume6
Issue number2
DOIs
StatePublished - Jan 1 2000

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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