| First Author | Ling BM | Year | 2012 |
| Journal | Mol Biol Cell | Volume | 23 |
| Issue | 24 | Pages | 4778-85 |
| PubMed ID | 23087213 | Mgi Jnum | J:200252 |
| Mgi Id | MGI:5507932 | Doi | 10.1091/mbc.E12-04-0311 |
| Citation | Ling BM, et al. (2012) G9a mediates Sharp-1-dependent inhibition of skeletal muscle differentiation. Mol Biol Cell 23(24):4778-85 |
| abstractText | Sharp-1, a basic helix-loop-helix transcription factor, is a potent repressor of skeletal muscle differentiation and is dysregulated in muscle pathologies. However, the mechanisms by which it inhibits myogenesis are not fully understood. Here we show that G9a, a lysine methyltransferase, is involved in Sharp-1-mediated inhibition of muscle differentiation. We demonstrate that G9a directly interacts with Sharp-1 and enhances its ability to transcriptionally repress the myogenin promoter. Concomitant with a differentiation block, G9a-dependent histone H3 lysine 9 dimethylation (H3K9me2) and MyoD methylation are apparent upon Sharp-1 overexpression in muscle cells. RNA interference-mediated reduction of G9a or pharmacological inhibition of its activity erases these repressive marks and rescues the differentiation defect imposed by Sharp-1. Our findings provide new insights into Sharp-1-dependent regulation of myogenesis and identify epigenetic mechanisms that could be targeted in myopathies characterized by elevated Sharp-1 levels. |
