title: Effects of myogenin on expression of late muscle genes through MyoD-dependent chromatin remodeling ability of myogenin.
abstract: MyoD and myogenin (Myog) recognize sets of distinct but overlapping target genes and play different roles in skeletal muscle differentiation. MyoD is sufficient for near-full expression of early targets, while Myog can only partially enhance expression of MyoD-initiated late muscle genes. However, the way in which Myog enhances the expression of MyoD-initiated late muscle genes remains unclear. Here, we examine the effects of Myog on chromatin remodeling at late muscle gene promoters and their activation within chromatin environment. Chromatin immunoprecipitation (ChIP) assay showed that Myog selectively bound to the regulatory sequences of late muscle genes. Overexpression of Myog was found to overcome sodium butyrateinhibited chromatin at late muscle genes in differentiating C2C12 myoblasts, shifting the transcriptional activation of these genes to an earlier time period. Furthermore, overexpression of Myog led to increased hyperacetylation of core histone H4 in differentiating C2C12 myoblasts but not NIH3T3 fibroblasts, and hyperacetylated H4 was associated directly with the late muscle genes in differentiating C2C12, indicating that Myog can induce chromatin remodeling in the presence of MyoD. In addition, co-immunoprecipitation (CoIP) revealed that Myog was associated with the nuclear protein Brd4 in differentiating C2C12 myoblasts. Together, these results suggest that Myog enhances the expression of MyoD-initiated late muscle genes through MyoD-dependent ability of Myog to induce chromatin remodeling, in which Myog-Brd4 interaction may be involved.
authors: Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing 100191, People's Republic of China.
authors: Chao
authors: C
authors: Du
authors: Ya-Qiong
authors: YQ
authors: Jin
authors: Jun-Juan
authors: JJ
authors: Qi
authors: Zhen-Xing
authors: ZX
authors: Ji
authors: Shu-Yan
authors: SY
authors: Li
authors: Guo-Shun
authors: GS
authors: An
authors: Hong-Ti
authors: HT
authors: Jia
authors: Ju-Hua
authors: JH
authors: Ni
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D047369:Chromatin Immunoprecipitation; D055785:Gene Knockdown Techniques; D006657:Histones / Q000235:genetics / Q000378:metabolism; D047468:Immunoprecipitation; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism / Q000502:physiology*; D017570:MyoD Protein / Q000235:genetics* / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology / Q000502:physiology; D018008:Myogenin / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D041681:NIH 3T3 Cells; D011401:Promoter Regions, Genetic; D015533:Transcriptional Activation
chemical_list: D002843:Chromatin; D006657:Histones; D017570:MyoD Protein; D018008:Myogenin