title: SH2B1 modulates chromatin state and MyoD occupancy to enhance expressions of myogenic genes.
abstract: As mesoderm-derived cell lineage commits to myogenesis, a spectrum of signaling molecules, including insulin growth factor (IGF), activate signaling pathways and ultimately instruct chromatin remodeling and the transcription of myogenic genes. MyoD is a key transcription factor during myogenesis. In this study, we have identified and characterized a novel myogenic regulator, SH2B1. Knocking down SH2B1 delays global chromatin condensation and decreases the formation of myotubes. SH2B1 interacts with histone H1 and is required for the removal of histone H1 from active transcription sites, allowing for the expressions of myogenic genes, IGF2 and MYOG. Chromatin immunoprecipitation assays suggest the requirement of SH2B1 for the induction of histone H3 lysine 4 trimethylation as well as the reduction of histone H3 lysine 9 trimethylation at the promoters and/or enhancers of IGF2 and MYOG genes during myogenesis. Furthermore, SH2B1 is required for the transcriptional activity of MyoD and MyoD occupancy at the enhancer/promoter regions of IGF2 and MYOG during myogenesis. Together, this study demonstrates that SH2B1 fine-tunes global-local chromatin states, expressions of myogenic genes and ultimately promotes myogenesis.
authors.affiliation: Institute of Molecular Medicine, National Tsing Hua University, Hsinchu, Taiwan, R.O.C.
authors.forename: Kuan-Wei
authors.initials: KW
authors.lastname: Chen
authors.affiliation: Institute of Molecular Medicine, National Tsing Hua University, Hsinchu, Taiwan, R.O.C.
authors.forename: Yu-Jung
authors.initials: YJ
authors.lastname: Chang
authors.affiliation: Department of Life Science, National Chung Cheng University, Chia-yi, Taiwan, R.O.C.
authors.forename: Chia-Ming
authors.initials: CM
authors.lastname: Yeh
authors.affiliation: Institute of Molecular Medicine, National Tsing Hua University, Hsinchu, Taiwan, R.O.C.
authors.forename: Yen-Ling
authors.initials: YL
authors.lastname: Lian
authors.affiliation: Department of Life Science, National Chung Cheng University, Chia-yi, Taiwan, R.O.C.
authors.forename: Michael W Y
authors.initials: MW
authors.lastname: Chan
authors.affiliation: Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan, R.O.C.
authors.forename: Cheng-Fu
authors.initials: CF
authors.lastname: Kao
authors.affiliation: Institute of Molecular Medicine, National Tsing Hua University, Hsinchu, Taiwan, R.O.C.; Department of Medical Science, National Tsing Hua University, Hsinchu, Taiwan, R.O.C.. Electronic address: lchen@life.nthu.edu.tw.
authors.forename: Linyi
authors.initials: L
authors.lastname: Chen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly / Q000235:genetics; D047369:Chromatin Immunoprecipitation / Q000379:methods; D004742:Enhancer Elements, Genetic / Q000235:genetics; D057809:HEK293 Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D008745:Methylation; D024510:Muscle Development / Q000235:genetics*; D017570:MyoD Protein / Q000378:metabolism*; D018008:Myogenin / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D015533:Transcriptional Activation / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002843:Chromatin; D006657:Histones; D017570:MyoD Protein; D018008:Myogenin; C518910:SH2B1 protein, human; D007335:Insulin-Like Growth Factor II
keywords: Chromatin; Differentiation; Histone modifications; Myogenesis; Transcriptional regulation