The expression of myogenic microRNAs indirectly requires protein arginine methyltransferase (Prmt)5 but directly requires Prmt4

Department of Cell Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
Nucleic Acids Research (Impact Factor: 9.11). 10/2010; 39(4):1243-55. DOI: 10.1093/nar/gkq896
Source: PubMed


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.

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