Open AccessG9a mediates Sharp-1–dependent inhibition of skeletal muscle differentiation
Author(s) -
Belinda Mei Tze Ling,
Suma Gopinadhan,
Wai Kay Kok,
Shilpa Rani Shankar,
Pooja Gopal,
Narendra Bharathy,
Yaju Wang,
Reshma Taneja
Publication year - 2012
Publication title -
molecular biology of the cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.463
H-Index - 225
eISSN - 1939-4586
pISSN - 1059-1524
DOI - 10.1091/mbc.e12-04-0311
Subject(s) - myogenesis , myod , myogenin , biology , myod protein , microbiology and biotechnology , transcription factor , epigenetics , repressor , myocyte , myf5 , skeletal muscle , myogenic regulatory factors , cellular differentiation , histone , genetics , endocrinology , gene
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.