Lysine methyltransferase G9a methylates the transcription factor MyoD and regulates skeletal muscle differentiation

Belinda Mei Tze Ling, Narendra Bharathy, Teng Kai Chung, Wai Kay Kok, Si De Li, Yong Hua Tan, Vinay Kumar Rao, Suma Gopinadhan, Vittorio Sartorelli, Martin J. Walsh, Reshma Taneja

Research output: Contribution to journalArticlepeer-review

121 Scopus citations


Skeletal muscle cells have served as a paradigm for understanding mechanisms leading to cellular differentiation. The proliferation and differentiation of muscle precursor cells require the concerted activity of myogenic regulatory factors including MyoD. In addition, chromatin modifiers mediate dynamic modifications of histone tails that are vital to reprogramming cells toward terminal differentiation. Here, we provide evidence for a unique dimension to epigenetic regulation of skeletal myogenesis. We demonstrate that the lysine methyltransferase G9a is dynamically expressed in myoblasts and impedes differentiation in a methyltransferase activity-dependent manner. In addition to mediating histone H3 lysine-9 di-methylation (H3K9me2) on MyoD target promoters, endogenous G9a interacts with MyoD in precursor cells and directly methylates it at lysine 104 (K104) to constrain its transcriptional activity. Mutation of K104 renders MyoD refractory to inhibition by G9a and enhances its myogenic activity. Interestingly, MyoD methylation is critical for G9a-mediated inhibition of myogenesis. These findings provide evidence of an unanticipated role for methyltransferases in cellular differentiation states by direct posttranslational modification of a transcription factor.

Original languageEnglish
Pages (from-to)841-846
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number3
StatePublished - 17 Jan 2012


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