Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/47643
Title: SHARP-1 REPRESSES MYOGENIC DIFFERENTIATION THROUGH RECRUITMENT OF METHYLTRANSFERASE G9A
Authors: LING MEI TZE, BELINDA
Keywords: Sharp-1, methyltransferase G9a, myogenesis.
Issue Date: 29-Jun-2012
Source: LING MEI TZE, BELINDA (2012-06-29). SHARP-1 REPRESSES MYOGENIC DIFFERENTIATION THROUGH RECRUITMENT OF METHYLTRANSFERASE G9A. ScholarBank@NUS Repository.
Abstract: Sharp-1, a basic helix-loop-helix (bHLH) transcription factor, functions as a potent repressor of skeletal muscle differentiation and is dysregulated in muscle pathologies. However, the mechanisms by which Sharp-1 inhibits myogenic differentiation are unclear. We have identified a lysine methyltransferase G9a as a novel co-factor that directly associates with Sharp-1, and is critical for Sharp-1-mediated repression of muscle differentiation. Similar to Sharp-1, G9a itself has an inhibitory role in skeletal myogenesis. In addition to mediating histone H3 lysine 9 di-methylation repression marks on muscle promoters, G9a methylates MyoD, a key transcription factor required for muscle development, at lysine (K104). Overexpression of Sharp-1 in muscle precursor cells, results in G9a-dependent histone modifications and MyoD methylation. siRNA-mediated knockdown of G9a or pharmacological blockage of its activity partially rescues the differentiation defects imposed by Sharp-1. Our findings provide new insights into Sharp-1-dependent regulation of myogenesis and identify epigenetic mechanisms which could be targeted in myopathies characterised by elevated Sharp-1 levels.
URI: http://scholarbank.nus.edu.sg/handle/10635/47643
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