Regulation of HDAC9 gene expression by MEF2 establishes a negative-feedback loop in the transcriptional circuitry of muscle differentiation

Michael Haberland, Michael A. Arnold, John McAnally, Dillon Phan, Yuri Kim, Eric N. Olson

Research output: Contribution to journalArticle

90 Scopus citations

Abstract

Skeletal muscle development is controlled by the myocyte enhancer factor (MEF2) and myogenic basic helix-loop-helix (bHLH) families of transcription factors, which associate and synergistically activate muscle gene expression. Muscle differentiation is further reinforced by positive-feedback loops in which myogenic bHLH proteins activate their own expression and the expression of MEF2, while MEF2 stimulates expression of myogenic bHLH genes and the Mef2c gene. Here we describe a myogenic negative-feedback loop that consists of MEF2 proteins and the transcriptional repressor histone deacetylase 9 (HDAC9). We show that the HDAC9 gene is a direct transcriptional target of MEF2 in vitro and in vivo. HDAC9 can associate with MEF2 proteins and suppress their transcriptional activity. The transcriptional repressor HDAC9 thus forms a negative-feedback loop in the transcriptional circuitry of muscle differentiation.

Original languageEnglish (US)
Pages (from-to)518-525
Number of pages8
JournalMolecular and cellular biology
Volume27
Issue number2
DOIs
StatePublished - Jan 1 2007

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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