biostudies-literatureLing BMIntramural NIH HHSNHLBI NIH HHSNCI NIH HHS841-6https://www.ebi.ac.uk/biostudies/studies/S-EPMC3271886biostudies-literatureUnknown109(3)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 Proceedings of the National Academy of Sciences of the United States of AmericaLysine methyltransferase G9a methylates the transcription factor MyoD and regulates skeletal muscle differentiation.PMC3271886R01 CA154809R01 HL103967Sartorelli VRao VKGopinadhan SLi SWalsh MJChung TKKok WKLing BMBharathy NTaneja RTan YHfalseLysine methyltransferase G9a methylates the transcription factor MyoD and regulates skeletal muscle differentiation.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 2012-01-01T00:00:00Z2012 Jan2025-04-19T08:03:46.334Z2019-03-27T00:48:42ZS-EPMC32718862221560010.1073/pnas.1111628109