title: The histone demethylase KDM4B interacts with MyoD to regulate myogenic differentiation in C2C12 myoblast cells.
abstract: Enzymes that mediate posttranslational modifications of histone and nonhistone proteins have been implicated in regulation of skeletal muscle differentiation. However, functions of histone demethylases that could counter the actions of H3-K9 specific histone methyltransferases remain still obscure. Here we present evidences that KDM4B histone demethylase regulates expression of myogenic regulators such as MyoD and thereby controls myogenic differentiation of C2C12 myoblast cells. We demonstrate that expression of KDM4B gradually increases during myogenic differentiation and depletion of KDM4B using shRNA results in inhibition of differentiation in C2C12 myoblast cells, which is correlated with decreased expression of MyoD and myogenin. In addition, we find that KDM4B shRNA represses expression of MyoD promoter-driven luciferase reporter and exogenous expression of MyoD rescues myogenic potential in KDM4B-depleted myoblast cells. We further show that KDM4B interacts with MyoD, binds to MyoD and myogenin promoters in vivo, and finally, is involved in demethylation of tri-methylated H3-K9 on promoters of MyoD and myogenin. Taken together, our data suggest that KDM4B plays key roles in myogenic differentiation of C2C12 cells, presumably by its function as a H3-K9 specific histone demethylase.
authors.affiliation: Department of Biological Sciences, College of Natural Science, Inha University, 253 Yonghyun-dong, Nam-Gu, Incheon 402-751, Republic of Korea.
authors.forename: Jang Hyun
authors.initials: JH
authors.lastname: Choi
authors.affiliation: Department of Biological Sciences, College of Natural Science, Inha University, 253 Yonghyun-dong, Nam-Gu, Incheon 402-751, Republic of Korea.
authors.forename: Young Joon
authors.initials: YJ
authors.lastname: Song
authors.affiliation: Department of Biological Sciences, College of Natural Science, Inha University, 253 Yonghyun-dong, Nam-Gu, Incheon 402-751, Republic of Korea. Electronic address: hlee@inha.ac.kr.
authors.forename: Hansol
authors.initials: H
authors.lastname: Lee
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D020869:Gene Expression Profiling; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D024510:Muscle Development / Q000235:genetics; D017570:MyoD Protein / Q000378:metabolism*; D032446:Myoblasts / Q000166:cytology* / Q000201:enzymology*; D018006:Myogenic Regulatory Factors / Q000378:metabolism; D011485:Protein Binding
chemical_list: D017570:MyoD Protein; D018006:Myogenic Regulatory Factors; D056484:Jumonji Domain-Containing Histone Demethylases; C511781:Kdm4b protein, mouse
keywords: Histone demethylase; KDM4B; MyoD; Myogenic differentiation