Regulation of MicroRNAs by brahma-related gene 1 (Brg1) in smooth muscle cells

Meng Chen, B. Herring

Research output: Contribution to journalArticle

11 Citations (Scopus)

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/SNFmediated chromatin remodeling thus regulates the phenotype of smooth muscle by affecting expression of protein-coding genes and microRNAs.

Original languageEnglish
Pages (from-to)6397-6408
Number of pages12
JournalJournal of Biological Chemistry
Volume288
Issue number9
DOIs
StatePublished - Mar 1 2013

Fingerprint

MicroRNAs
Smooth Muscle Myocytes
Muscle
Genes
Cells
Serum Response Factor
Chromatin Assembly and Disassembly
Chromatin
Smooth Muscle
Phenotype
Null Lymphocytes
Gene Knockout Techniques
myocardin
Chromatin Immunoprecipitation
Transcription
Microarrays
Ablation
Assays

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Regulation of MicroRNAs by brahma-related gene 1 (Brg1) in smooth muscle cells. / Chen, Meng; Herring, B.

In: Journal of Biological Chemistry, Vol. 288, No. 9, 01.03.2013, p. 6397-6408.

Research output: Contribution to journalArticle

Chen, Meng ; Herring, B. / Regulation of MicroRNAs by brahma-related gene 1 (Brg1) in smooth muscle cells. In: Journal of Biological Chemistry. 2013 ; Vol. 288, No. 9. pp. 6397-6408.
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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/SNFmediated chromatin remodeling thus regulates the phenotype of smooth muscle by affecting expression of protein-coding genes and microRNAs.",
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