title: The SWI/SNF chromatin remodeling complex regulates myocardin-induced smooth muscle-specific gene expression.
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.
  
  
  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.
authors.affiliation: Department of Cellular and Integrative Physiology, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, IN 46202-5120, USA.
authors.forename: Jiliang
authors.initials: J
authors.lastname: Zhou
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.forename: Hong
authors.initials: H
authors.lastname: Fang
authors.forename: Omar
authors.initials: O
authors.lastname: El-Mounayri
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Rodenberg
authors.forename: Anthony N
authors.initials: AN
authors.lastname: Imbalzano
authors.forename: B Paul
authors.initials: BP
authors.lastname: Herring