Skeletal muscle specification by myogenin and Mef2D via the SWI/SNF ATPase Brg1.
Myogenin is required not for the initiation of myogenesis but instead for skeletal muscle formation through poorly understood mechanisms. We demonstrate in cultured cells and, for the first time, in embryonic tissue, that myogenic late genes that specify the skeletal muscle phenotype are bound by MyoD prior to the initiation of gene expression. At the onset of muscle specification, a transition from MyoD to myogenin occurred at late gene loci, concomitant with loss of HDAC2, the appearance of both the Mef2D regulator and the Brg1 chromatin-remodeling enzyme, and the opening of chromatin structure. We further demonstrated that ectopic expression of myogenin and Mef2D, in the absence of MyoD, was sufficient to induce muscle differentiation in a manner entirely dependent on Brg1. These results indicate that myogenin specifies the muscle phenotype by cooperating with Mef2D to recruit an ATP-dependent chromatin-remodeling enzyme that alters chromatin structure at regulatory sequences to promote terminal differentiation.
Ohkawa
Yasuyuki
Y
Department of Cell Biology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Marfella
Concetta G A
CG
Imbalzano
Anthony N
AN
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D042002:Chromatin Assembly and Disassembly; D004265:DNA Helicases; D005260:Female; D018507:Gene Expression Regulation, Developmental; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases / Q000378:metabolism; D064326:MEF2 Transcription Factors; D051379:Mice; D008810:Mice, Inbred C57BL; D024510:Muscle Development / Q000502:physiology; D018482:Muscle, Skeletal / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D017570:MyoD Protein / Q000378:metabolism; D051787:Myogenic Regulatory Factor 5 / Q000378:metabolism; D018006:Myogenic Regulatory Factors / Q000378:metabolism / Q000502:physiology*; D018008:Myogenin / Q000502:physiology*; D009687:Nuclear Proteins / Q000378:metabolism / Q000502:physiology*; D012097:Repressor Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*
D064326:MEF2 Transcription Factors; C578044:Mef2d protein, mouse; C497418:Myf5 protein, mouse; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D051787:Myogenic Regulatory Factor 5; D018006:Myogenic Regulatory Factors; D018008:Myogenin; D009687:Nuclear Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D000255:Adenosine Triphosphate; C533424:Hdac2 protein, mouse; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases; C513194:Smarca4 protein, mouse; D004265:DNA Helicases