title: A role for histone deacetylase HDAC1 in modulating the transcriptional activity of MyoD: inhibition of the myogenic program.
abstract: The molecular mechanism(s) that are responsible for suppressing MyoD's transcriptional activities in undifferentiated skeletal muscle cells have not yet been determined. We now show that MyoD associates with a histone deacetylase-1 (HDAC1) in these cells and that this interaction is responsible for silencing MyoD-dependent transcription of endogenous p21 as well as muscle-specific genes. Specifically, we present evidence that HDAC1 can bind directly to MyoD and use an acetylated MyoD as a substrate in vitro, whereas a mutant version of HDAC1 (H141A) can not. Further more, this mutant also fails to repress MyoD-mediated transcription in vivo, and unlike wild-type HDAC1 it can not inhibit myogenic conversion, as judged by confocal microscopy. Finally, we show that an endogenous MyoD can be acetylated upon its conversion to a hypophosphorylated state and only when the cells have been induced to differentiate. These results provide for a model which postulates that MyoD may be co-dependent on HDAC1 and P/CAF for temporally controlling its transcriptional activity before and after the differentiation of muscle cells.
authors: Department of Molecular Biology, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
authors: A
authors: A
authors: Mal
authors: M
authors: M
authors: Sturniolo
authors: R L
authors: RL
authors: Schiltz
authors: M K
authors: MK
authors: Ghosh
authors: M L
authors: ML
authors: Harter
mesh_terms: D000107:Acetylation; D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D002461:Cell Line, Transformed; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics; D051548:Histone Acetyltransferases; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology*; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors; D014158:Transcription, Genetic; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
chemical_list: D000123:Acetyltransferases; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D051548:Histone Acetyltransferases; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases; D017570:MyoD Protein; D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C493956:CDKN1A protein, human; C493957:Cdkn1a protein, mouse; C110550:HDAC1 protein, human