The role of Brahma‐related gene 1 in regulating the expression of microRNAs in colonic smooth muscle cells

Abstract

To identify microRNAs (miRs) that are regulated by Brahmarelated gene 1 (Brg1) in smooth muscle cells (SMCs), we performed microRNA array screens of colonic smooth muscle. Quantitative reverse transcription‐polymerase chain reaction assays confirmed that 6 miRs were down‐regulated and 6 up‐regulated in smooth muscle specific Brg1 knockout tissue. Inactivation of endogenous Brg1 by introducing dominant negative Brg1 into wild type SMCs in vitro, revealed that miR‐143/145 are likely to be directly regulated by Brg1 in smooth muscle cells. miR‐143/145 have been previously shown to be regulated by myocardin and to be important for regulating the phenotype of smooth muscle cells. In Brg1 null SW13 cells, miR‐143/145 were dramatically induced by myocardin only in the presence of Brg1. Chromatin immunoprecipitation assays demonstrated that myocardin increased the binding of serum response factor to the miR‐143/145 promoter only in the presence of Brg1. Together these data suggest a mechanism in which Brg1 containing SWI/SNF complexes are required for myocardin to induce expression of miR‐143/145 in smooth muscle. This suggests that SWI/SNF mediated chromatin remodeling regulates the phenotype of smooth muscle not only by directly affecting expression of smooth muscle specific genes, but also by regulating expression of microRNAs that further modulate expression of their targets.Supported by NIH DK61130.