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The regulation of microRNAs by Brahma‐related gene 1 in smooth muscle cells
Author(s) -
Chen Meng,
Herring Paul
Publication year - 2013
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.27.1_supplement.770.5
Subject(s) - myocardin , gene knockdown , microrna , swi/snf , chromatin immunoprecipitation , serum response factor , epigenetics , chromatin remodeling , gene expression , chromatin , regulation of gene expression , microbiology and biotechnology , biology , gene , genetics , promoter
MicroRNAs (miRs) regulate the phenotypic switch of smooth muscle cells (SMCs) that occurs under pathological conditions. Little is known about the transcriptional and epigenetic regulation of miR expression in SMCs. To identify miRs that are regulated by the Brahma‐related gene 1 (Brg1)‐containing SWI/SNF chromatin remodeling complex we performed a microRNA array screen of RNA isolated from colonic SMCs of mice harboring a smooth muscle‐specific knockout of Brg1. Quantitative RT‐PCR confirmed changes in expression of several miRs, including miRs‐143/5 and miR‐133. Expression of dominant negative Brg1 in wild‐type SMCs led to decreased expression of miRs‐143/145 but not miR‐133. The dominant negative Brg1 also blocked the myocardin‐mediated induction of miRs‐143/5 in 10T1/2 cells. Knockdown of SRF or myocardin decreased expression of miRs‐143/5 in SMCs, whereas miR‐133 expression was only repressed following SRF knockdown. In Brg1‐null SW13 cells, miRs‐143/5 but not miR‐133 were dramatically induced by myocardin only in the presence of Brg1. Chromatin immunoprecipitation assays revealed that Brg1 was important for myocardin‐mediated SRF binding to the miRs‐143/5 promoter. These data show that Brg1‐dependent chromatin remodeling regulates the expression of miRs‐143/5 and miR‐133 through distinct pathways in SMCs. Supported by NIH DK61130 and AHA predoctoral fellowship.