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

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


  • Zhou J
  • Zhang M
  • Fang H
  • El-Mounayri O
  • Rodenberg JM
  • Imbalzano AN
  • Herring BP


Arteriosclerosis, thrombosis, and vascular biology

Publication Data

June 21, 2009

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

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