Myogenic differentiation requires the coordination between permanent cell cycle withdrawal, mediated by members of the cyclin-dependent kinase inhibitor (CKI) family, and activation of a cascade of myogenic transcription factors, particularly MYOGENIN (MYOG). Recently, it has been reported that the Protein aRginine Methyl Transferase PRMT5 modulates the early phase of induction of MYOG expression. Here, we show that the histone- and PRMT5-associated protein COPR5 (cooperator of PRMT5) is required for myogenic differentiation. C2C12 cells, in which COPR5 had been silenced, could not irreversibly exit the cell cycle and differentiate into muscle cells. This phenotype might be explained by the finding that, in cells in which COPR5 was downregulated, p21 and MYOG induction was strongly reduced and PRMT5 recruitment to the promoters of these genes was also altered. Moreover, we suggest that COPR5 interaction with the Runt-related transcription factor 1 (RUNX1)-core binding factor-beta (CBFbeta) complex contributes to targeting the COPR5-PRMT5 complex to these promoters. Finally, we present evidence that COPR5 depletion delayed the in vivo regeneration of cardiotoxin-injured mouse skeletal muscles. Altogether, these data extend the role of COPR5 from an adaptor protein required for nuclear functions of PRMT5 to an essential coordinator of myogenic differentiation.
The histone- and PRMT5-associated protein COPR5 is required for myogenic differentiation
Paul, C.; Sardet, C.; Fabbrizio, E.
Cell Death Differ
2012-05 / vol 19 / pages 900-8
10.1038/cdd.2011.193 cdd2011193 [pii]
1476-5403 (Electronic) 1350-9047 (Linking)
Animals; Mice; Chromatin Immunoprecipitation; Promoter Regions, Genetic/genetics; Flow Cytometry; Cell Line; Blotting, Western; Cell Cycle/genetics/physiology; Cell Differentiation/genetics/physiology; Cobra Cardiotoxin Proteins/toxicity; Core Binding Factor beta Subunit/genetics/metabolism; Crotoxin/toxicity; Drug Combinations; Intracellular Signaling Peptides and Proteins/genetics/metabolism; Muscle, Skeletal/drug effects/injuries/metabolism; Myogenin/genetics/metabolism; Nuclear Proteins/genetics/*metabolism; Protein Binding/genetics/physiology; Protein Methyltransferases/genetics/*metabolism; Protein-Arginine N-Methyltransferases/genetics/metabolism