title: The transcription factor TEAD1 represses smooth muscle-specific gene expression by abolishing myocardin function.
abstract: The TEAD (transcriptional enhancer activator domain) proteins share an evolutionarily conserved DNA-binding TEA domain, which binds to the MCAT cis-acting regulatory element. Previous studies have shown that TEAD proteins are involved in regulating the expression of smooth muscle α-actin. However, it remains undetermined whether TEAD proteins play a broader role in regulating expression of other genes in vascular smooth muscle cells. In this study, we show that the expression of TEAD1 is significantly induced during smooth muscle cell phenotypic modulation and negatively correlates with smooth muscle-specific gene expression. We further demonstrate that TEAD1 plays a novel role in suppressing expression of smooth muscle-specific genes, including smooth muscle α-actin, by abolishing the promyogenic function of myocardin, a key mediator of smooth muscle differentiation. Mechanistically, we found that TEAD1 competes with myocardin for binding to serum response factor (SRF), resulting in disruption of myocardin and SRF interactions and thereby attenuating expression of smooth muscle-specific genes. This study provides the first evidence demonstrating that TEAD1 is a novel general repressor of smooth muscle-specific gene expression through interfering with myocardin binding to SRF.
authors.affiliation: From the Department of Pharmacology and Toxicology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia 30912 and.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Wang
authors.forename: Guoqing
authors.initials: G
authors.lastname: Hu
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: Jiliang
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000235:genetics; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D009928:Organ Specificity; D051381:Rats; D012097:Repressor Proteins / Q000378:metabolism*; D026362:Serum Response Factor / Q000235:genetics / Q000378:metabolism; D000091262:TEA Domain Transcription Factors; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000099251:Myocardin
chemical_list: D004268:DNA-Binding Proteins; D009124:Muscle Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D026362:Serum Response Factor; D000091262:TEA Domain Transcription Factors; D015534:Trans-Activators; D014157:Transcription Factors; D000099251:Myocardin; C057182:TEAD1 protein, human
keywords: Smooth Muscle; Smooth Muscle Phenotypic Modulation; TEAD1; Tissue-specific Transcription Factors; Transcription Factors; Transcriptional regulation; Vascular Biology; Vascular Smooth Muscle Cells