The expression of myogenic microRNAs indirectly requires protein arginine methyltransferase (Prmt)5 but directly requires Prmt4.
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.
Department of Cell Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
Chandrashekara
C
Mallappa
Yu-Jie
YJ
Hu
Priscilla
P
Shamulailatpam
Sookil
S
Tae
Saïd
S
Sif
Anthony N
AN
Imbalzano
D000818:Animals; D004265:DNA Helicases / Q000378:metabolism; D015870:Gene Expression; D007700:Kinetics; D051379:Mice; D035683:MicroRNAs / Q000737:chemistry / Q000378:metabolism*; D024510:Muscle Development / Q000235:genetics; D018482:Muscle, Skeletal / Q000378:metabolism; D018008:Myogenin / Q000378:metabolism; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000378:metabolism; D011496:Protein Methyltransferases / Q000502:physiology*; D011484:Protein-Arginine N-Methyltransferases / Q000502:physiology*; D038621:Regulatory Sequences, Ribonucleic Acid; D014157:Transcription Factors / Q000378:metabolism
D035683:MicroRNAs; C517732:Mirn133 microRNA, mouse; D018008:Myogenin; D009687:Nuclear Proteins; D038621:Regulatory Sequences, Ribonucleic Acid; D014157:Transcription Factors; D011496:Protein Methyltransferases; C498518:Prmt5 protein, mouse; D011484:Protein-Arginine N-Methyltransferases; C119966:coactivator-associated arginine methyltransferase 1; C513194:Smarca4 protein, mouse; D004265:DNA Helicases