title: The histone methyltransferase Set7/9 promotes myoblast differentiation and myofibril assembly.
abstract: The molecular events that modulate chromatin structure during skeletal muscle differentiation are still poorly understood. We report in this paper that expression of the H3-K4 histone methyltransferase Set7 is increased when myoblasts differentiate into myotubes and is required for skeletal muscle development, expression of muscle contractile proteins, and myofibril assembly. Knockdown of Set7 or expression of a dominant-negative Set7 mutant impairs skeletal muscle differentiation, accompanied by a decrease in levels of histone monomethylation (H3-K4me1). Set7 directly interacts with MyoD to enhance expression of muscle differentiation genes. Expression of myocyte enhancer factor 2 and genes encoding contractile proteins is decreased in Set7 knockdown myocytes. Furthermore, we demonstrate that Set7 also activates muscle gene expression by precluding Suv39h1-mediated H3-K9 methylation on the promoters of myogenic differentiation genes. Together, our experiments define a biological function for Set7 in muscle differentiation and provide a molecular mechanism by which Set7 modulates myogenic transcription factors during muscle differentiation.
authors.affiliation: McAllister Heart Institute, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Yazhong
authors.initials: Y
authors.lastname: Tao
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Neppl
authors.forename: Zhan-Peng
authors.initials: ZP
authors.lastname: Huang
authors.forename: Jianfu
authors.initials: J
authors.lastname: Chen
authors.forename: Ru-Hang
authors.initials: RH
authors.lastname: Tang
authors.forename: Ru
authors.initials: R
authors.lastname: Cao
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Suk-Won
authors.initials: SW
authors.lastname: Jin
authors.forename: Da-Zhi
authors.initials: DZ
authors.lastname: Wang
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D042002:Chromatin Assembly and Disassembly; D005347:Fibroblasts / Q000201:enzymology; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D064326:MEF2 Transcription Factors; D008745:Methylation; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D024510:Muscle Development / Q000235:genetics; D009154:Mutation; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism; D032448:Myoblasts, Skeletal / Q000201:enzymology*; D009210:Myofibrils / Q000201:enzymology*; D018006:Myogenic Regulatory Factors / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D006657:Histones; D064326:MEF2 Transcription Factors; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D018006:Myogenic Regulatory Factors; D012097:Repressor Proteins; D029961:Zebrafish Proteins; C498700:Suv39h1 protein, mouse; D008780:Methyltransferases; D011495:Histone-Lysine N-Methyltransferase