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A novel role of Brg1 in the regulation of SRF/MRTFA‐dependent smooth muscle‐specific genes
Author(s) -
Zhang Min,
Fang Hong,
Zhou Jiliang,
Herring Paul
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a654-c
Subject(s) - serum response factor , myocardin , chromatin immunoprecipitation , transcription factor , gene , microbiology and biotechnology , swi/snf , promoter , chromatin , gene expression , regulation of gene expression , endogeny , biology , chemistry , chromatin remodeling , genetics , biochemistry
Serum Response Factor (SRF) has been shown to be a key regulator of smooth muscle (SM) differentiation, proliferation and migration, via its interaction with accessory proteins. Myocardin Related Transcription Factor A (MRTFA) is a co‐activator of SRF that can induce expression of SRF‐dependent, smooth muscle‐specific genes and actin/Rho‐dependent genes. How MRTFA and SRF discriminate between these sets of target genes is still unclear. We hypothesized that the ATP‐dependent chromatin remodeling enzymes, Brahma‐Related Gene1 (Brg1) and Brahma (Brm), may play a role in this process. Western blotting and qRT‐PCR analysis demonstrated that dominant negative Brg1 blocked the ability of MRTFA to induce the expression of SM genes, but not actin/Rho‐dependent genes. MRTFA over‐expression could not induce SM gene expression in Sw13 cells, which lack endogenous Brg1 or Brm. Reintroduction of Brg1 or Brm into Sw13 cells restored their responsiveness to MRTFA. Co‐IP data showed that Brg1, SRF and MRTFA form a complex in vivo . Chromatin immunoprecipitation assays suggest that DN‐Brg1 significantly attenuates the ability of MRTFA to increase SRF binding to the promoters of smooth muscle‐specific genes. Together these data suggest that Brg1 plays a critical role in regulating expression of SRF and MRTFA dependent smooth muscle‐specific genes but is not required for SRF and MRTFA to induce expression of immediate early genes.