Modulation of smooth muscle gene expression by association of histone acetyltransferases and deacetylases with myocardin.
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.
Cao
Dongsun
D
Department of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390-9148, USA.
Wang
Zhigao
Z
Zhang
Chun-Li
CL
Oh
Jiyeon
J
Xing
Weibing
W
Li
Shijie
S
Richardson
James A
JA
Wang
Da-Zhi
DZ
Olson
Eric N
EN
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
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