UMMS Affiliation

Department of Cell Biology

Date

3-17-2011

Document Type

Article

Medical Subject Headings

Protein Methyltransferases; Myogenic Regulatory Factors; Myogenin; MicroRNAs

Disciplines

Cell Biology

Abstract

Myogenic microRNAs are important regulators of muscle development and differentiation. To better understand the roles of chromatin-modifying and remodeling enzymes in the activation of myogenic microRNA expression, we have functionally analyzed two different protein arginine methyltransferases, Prmt5 and Prmt4, both of which have previously been implicated in the regulation of myogenic mRNA expression. Both Prmts are required for myogenic microRNA induction during differentiation. Prmt5 is indirectly required due to the necessity of Prmt5 for expression of the transcriptional regulator, myogenin, as ectopic expression of myogenin eliminates Prmt5 dependency. By contrast, Prmt4 binds to the upstream regulatory regions of myogenic microRNAs and is required for dimethylation of the Prmt4 substrate, H3R17, at microRNA regulatory sequences. Deletion of Prmt4 does not alter MyoD binding at myogenic microRNA regulatory sequences but prevents the binding of both myogenin and the Brg1 ATPase that catalyzes SWI/SNF-dependent chromatin remodeling, resulting in an inhibition of microRNA expression.

Rights and Permissions

Citation: Nucleic Acids Res. 2011 Mar 1;39(4):1243-55. Epub 2010 Oct 14. doi: 10.1093/nar/gkq896. Link to article on publisher's site

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Link to Article in PubMed

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