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

http://www.ncbi.nlm.nih.gov/pubmed/19342595

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. CONCLUSIONS: 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.

Pubmed ID: 19342595 RIS Download

Mesh terms: Animals | Cell Differentiation | Cells, Cultured | Chromatin Assembly and Disassembly | DNA Helicases | Gene Expression Regulation | Humans | Mice | Muscle Development | Muscle, Smooth, Vascular | Mutation | Nuclear Proteins | Promoter Regions, Genetic | Protein Binding | Protein Structure, Tertiary | RNA Interference | RNA, Small Interfering | Serum Response Factor | Trans-Activators | Transcription Factors | Transfection

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Associated grants

  • Agency: NIDDK NIH HHS, Id: DK61130
  • Agency: NIDDK NIH HHS, Id: DK65644
  • Agency: NIGMS NIH HHS, Id: GM56244
  • Agency: NHLBI NIH HHS, Id: HL58571
  • Agency: NIDDK NIH HHS, Id: R01 DK061130
  • Agency: NIDDK NIH HHS, Id: R01 DK061130-05
  • Agency: NIDDK NIH HHS, Id: R01 DK061130-06A2
  • Agency: NIGMS NIH HHS, Id: R01 GM056244
  • Agency: NIGMS NIH HHS, Id: R01 GM056244-12

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