The SWI/SNF chromatin remodeling complex regulates myocardin-induced smooth muscle-specific gene expression

Jiliang Zhou, Min Zhang, Hong Fang, Omar El-Mounayri, Jennifer M. Rodenberg, Anthony N. Imbalzano, B. Paul Herring

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

OBJECTIVE-: Regulatory complexes comprising myocardin and serum response factor (SRF) are critical for the transcriptional regulation of many smooth muscle-specific genes. However, little is known about the epigenetic mechanisms that regulate the activity of these complexes. In the current study, we investigated the role of SWI/SNF ATP-dependent chromatin remodeling enzymes in regulating the myogenic activity of myocardin. METHODS AND RESULTS-: We found that both Brg1 and Brm are required for maintaining expression of several smooth muscle-specific genes in primary cultures of aortic smooth muscle cells. Furthermore, the ability of myocardin to induce expression of smooth muscle-specific genes is abrogated in cells expressing dominant negative Brg1. In SW13 cells, which lack endogenous Brg1 and Brm1, myocardin is unable to induce expression of smooth muscle-specific genes. Whereas, reconstitution of wild-type, or bromodomain mutant forms Brg1 or Brm1, into SW13 cells restored their responsiveness to myocardin. SWI/SNF complexes were found to be required for myocardin to increase SRF binding to the promoters of smooth muscle-specific genes. Brg1 and Brm directly bind to the N terminus of myocardin, in vitro, through their ATPase domains and Brg1 forms a complex with SRF and myocardin in vivo in smooth muscle cells. CONCLUSION-: These data demonstrate that the ability of myocardin to induce smooth muscle-specific gene expression is dependent on its interaction with SWI/SNF ATP-dependent chromatin remodeling complexes.

Original languageEnglish (US)
Pages (from-to)921-928
Number of pages8
JournalArteriosclerosis, thrombosis, and vascular biology
Volume29
Issue number6
DOIs
StatePublished - Jun 1 2009

Keywords

  • Brg1
  • Brm
  • Calponin
  • SRF
  • Telokin

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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