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

ABSTRACT: 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.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.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.

SUBMITTER: Zhou J

PROVIDER: S-EPMC2730881 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature

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

Zhou Jiliang J Zhang Min M Fang Hong H El-Mounayri Omar O Rodenberg Jennifer M JM Imbalzano Anthony N AN Herring B Paul BP

Arteriosclerosis, thrombosis, and vascular biology 20090402 6

<h4>Objective</h4>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.<h4>Methods and results</h4>We found that both Brg1 and Brm are requ ...[more]

PMID: 19342595

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Dataset Information

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

Publications

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

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