title: The methyl-CpG-binding protein CIBZ suppresses myogenic differentiation by directly inhibiting myogenin expression.
abstract: Postnatal growth and regeneration of skeletal muscle are carried out mainly by satellite cells, which, upon stimulation, begin to express myogenin (Myog), the critical determinant of myogenic differentiation. DNA methylation status has been associated with the expression of Myog, but the causative mechanism remains almost unknown. Here, we report that the level of CIBZ, a methyl-CpG-binding protein, decreases upon myogenic differentiation of satellite-derived C2C12 cells, and during skeletal muscle regeneration in mice. We present data showing that the loss of CIBZ promotes myogenic differentiation, whereas exogenous expression of CIBZ impairs it, in cultured cells. CIBZ binds to a Myog promoter-proximal region and inhibits Myog transcription in a methylation-dependent manner. These data suggest that the suppression of myogenic differentiation by CIBZ is dependent, at least in part, on the regulation of Myog. Our data show that the methylation status of this proximal Myog promoter inversely correlates with Myog transcription in cells and tissues, and during postnatal growth of skeletal muscle. Notably, induction of Myog transcription by CIBZ suppression is independent of the demethylation of CpG sites in the Myog promoter. These observations provide the first reported molecular mechanism illustrating how Myog transcription is coordinately regulated by a methyl-CpG-binding protein and the methylation status of the proximal Myog promoter.
authors.affiliation: Division of Gene Function in Animals, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0192, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Oikawa
authors.forename: Reiko
authors.initials: R
authors.lastname: Omori
authors.forename: Tomonori
authors.initials: T
authors.lastname: Nishii
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Ishida
authors.forename: Masashi
authors.initials: M
authors.lastname: Kawaichi
authors.forename: Eishou
authors.initials: E
authors.lastname: Matsuda
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D018899:CpG Islands; D019175:DNA Methylation; D015536:Down-Regulation; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology* / Q000378:metabolism; D018008:Myogenin / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D012038:Regeneration; D012097:Repressor Proteins / Q000378:metabolism*
chemical_list: C510763:Zbtb38 protein, mouse; C503801:Myog protein, mouse; D018008:Myogenin; D034741:RNA, Small Interfering; D012097:Repressor Proteins