title: Acetylation of myocardin is required for the activation of cardiac and smooth muscle genes.
abstract: Myocardin belongs to the SAF-A/B, Acinus, PIAS (SAP) domain family of transcription factors and is specifically expressed in cardiac and smooth muscle. Myocardin functions as a transcriptional coactivator of SRF and is sufficient and necessary for smooth muscle gene expression. We have previously found that myocardin induces the acetylation of nucleosomal histones surrounding SRF-binding sites in the control regions of cardiac and smooth muscle genes through recruiting chromatin-modifying enzyme p300, yet no studies have determined whether myocardin itself is similarly modified. In this study, we show that myocardin is a direct target for p300-mediated acetylation. p300 acetylates lysine residues at the N terminus of the myocardin protein. Interestingly, a direct interaction between p300 and myocardin, which is mediated by the C terminus of myocardin, is required for the acetylation event. Acetylation of myocardin by p300 enhances the association of myocardin and SRF as well as the formation of the myocardin-SRF-CArG box ternary complex. Conversely, acetylation of myocardin decreases the binding of histone deacetylase 5 (HDAC5) to myocardin. Acetylation of myocardin is required for myocardin to activate smooth muscle genes. Our study demonstrates that acetylation plays a key role in modulating myocardin function in controlling cardiac and smooth muscle gene expression.
authors.affiliation: Department of Cardiology, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Dongsun
authors.initials: D
authors.lastname: Cao
authors.forename: Chunbo
authors.initials: C
authors.lastname: Wang
authors.forename: Ruhang
authors.initials: R
authors.lastname: Tang
authors.forename: Huaqun
authors.initials: H
authors.lastname: Chen
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Mariko
authors.initials: M
authors.lastname: Tatsuguchi
authors.forename: Da-Zhi
authors.initials: DZ
authors.lastname: Wang
mesh_terms: D000107:Acetylation; D000818:Animals; D019556:COS Cells; D002843:Chromatin / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006657:Histones / Q000235:genetics; D051379:Mice; D008954:Models, Biological; D009130:Muscle, Smooth / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D026362:Serum Response Factor / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*; D015533:Transcriptional Activation; D050880:p300-CBP Transcription Factors / Q000378:metabolism; D000099251:Myocardin
chemical_list: D002843:Chromatin; D006657:Histones; D009687:Nuclear Proteins; D026362:Serum Response Factor; D015534:Trans-Activators; D050880:p300-CBP Transcription Factors; D000099251:Myocardin