title: Regulation of microRNAs by Brahma-related gene 1 (Brg1) in smooth muscle cells.
abstract: MicroRNAs are involved in phenotypic switching of smooth muscle cells (SMCs). Brg1-containing SWI/SNF chromatin-remodeling complexes also play an important role in controlling the phenotype of SMCs. We thus determined whether Brg1 influences the transcription of microRNAs in SMCs. Microarray and quantitative RT-PCR analysis of smooth muscle from mice harboring smooth muscle-specific deletion of Brg1 revealed altered expression of several microRNAs, including miRs-143/145 and miR-133. Ablation of Brg1 in SMCs in vitro either by expression of dominant negative Brg1 or Brg1 knock-out attenuated miRs-143/145 expression. Knockdown of serum response factor (SRF) in SMCs significantly reduced the expression levels of miRs-143/145 and miR-133, whereas knockdown of myocardin only attenuated miRs-143/145 expression. Myocardin induced expression of miRs-143/145 and miR-133a and increased SRF binding to these genes in 10T1/2 cells. This myocardin-mediated induction was attenuated by dominant negative Brg1. In Brg1-null SW13 cells, miRs-143/145 were dramatically induced by myocardin only in the presence of Brg1, whereas miR-133 was not induced by myocardin in a Brg1-dependent manner. Chromatin immunoprecipitation assays demonstrated that in the presence of Brg1, myocardin increased SRF binding to both the miRs-143/145 and miR-133a loci. Together, these data suggest a mechanism in which Brg1-containing SWI/SNF complexes are required for myocardin to induce expression of miRs-143/145 in smooth muscle cells. In contrast, miR-133 expression appears to be regulated by Brg1-containing chromatin remodeling complexes in a partially SRF-dependent, although largely myocardin-independent manner. SWI/SNF-mediated chromatin remodeling thus regulates the phenotype of smooth muscle by affecting expression of protein-coding genes and microRNAs.
authors: Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
authors: Meng
authors: M
authors: Chen
authors: B Paul
authors: BP
authors: Herring
mesh_terms: D000818:Animals; D042002:Chromatin Assembly and Disassembly / Q000502:physiology*; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism*; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D026362:Serum Response Factor / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000099251:Myocardin
chemical_list: D004265:DNA Helicases; D035683:MicroRNAs; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; D026362:Serum Response Factor; D015534:Trans-Activators; D014157:Transcription Factors; D000099251:Myocardin; C476858:SRF protein, human; C084108:SMARCA4 protein, human; C513194:Smarca4 protein, mouse