title: Modulation of smooth muscle gene expression by association of histone acetyltransferases and deacetylases with myocardin.
abstract: Differentiation of smooth muscle cells is accompanied by the transcriptional activation of an array of muscle-specific genes controlled by serum response factor (SRF). Myocardin is a cardiac and smooth muscle-specific expressed transcriptional coactivator of SRF and is sufficient and necessary for smooth muscle gene expression. Here, we show that myocardin induces the acetylation of nucleosomal histones surrounding SRF-binding sites in the control regions of smooth muscle genes. The promyogenic activity of myocardin is enhanced by p300, a histone acetyltransferase that associates with the transcription activation domain of myocardin. Conversely, class II histone deacetylases interact with a domain of myocardin distinct from the p300-binding domain and suppress smooth muscle gene activation by myocardin. These findings point to myocardin as a nexus for positive and negative regulation of smooth muscle gene expression by changes in chromatin acetylation.
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390-9148, USA.
authors.forename: Dongsun
authors.initials: D
authors.lastname: Cao
authors.forename: Zhigao
authors.initials: Z
authors.lastname: Wang
authors.forename: Chun-Li
authors.initials: CL
authors.lastname: Zhang
authors.forename: Jiyeon
authors.initials: J
authors.lastname: Oh
authors.forename: Weibing
authors.initials: W
authors.lastname: Xing
authors.forename: Shijie
authors.initials: S
authors.lastname: Li
authors.forename: James A
authors.initials: JA
authors.lastname: Richardson
authors.forename: Da-Zhi
authors.initials: DZ
authors.lastname: Wang
authors.forename: Eric N
authors.initials: EN
authors.lastname: Olson
mesh_terms: D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D002319:Cardiovascular System / Q000166:cytology; D018797:Cell Cycle Proteins / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D005786:Gene Expression Regulation; D005982:Glutathione Transferase / Q000378:metabolism; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D047468:Immunoprecipitation; D007763:Lac Operon; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008957:Models, Genetic; D009130:Muscle, Smooth / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000166:cytology; D009687:Nuclear Proteins / Q000378:metabolism*; D009707:Nucleosomes / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; D000099251:Myocardin
chemical_list: D000123:Acetyltransferases; D018797:Cell Cycle Proteins; D002843:Chromatin; D005982:Glutathione Transferase; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases; D006657:Histones; D008156:Luciferases; D009687:Nuclear Proteins; D009707:Nucleosomes; D015534:Trans-Activators; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; D000099251:Myocardin