MCAT elements and the TEF-1 family of transcription factors in muscle development and disease.
MCAT elements are located in the promoter-enhancer regions of cardiac, smooth, and skeletal muscle-specific genes including cardiac troponin T, beta-myosin heavy chain, smooth muscle alpha-actin, and skeletal alpha-actin, and play a key role in the regulation of these genes during muscle development and disease. The binding factors of MCAT elements are members of the transcriptional enhancer factor-1 (TEF-1) family. However, it has not been fully understood how these transcription factors confer cell-specific expression in muscle, because their expression patterns are relatively broad. Results of recent studies revealed multiple mechanisms whereby TEF-1 family members control MCAT element-dependent muscle-specific gene expression, including posttranslational modifications of TEF-1 family members, the presence of muscle-selective TEF-1 cofactors, and cell-selective control of TEF-1 accessibility to MCAT elements. In addition, of particular interest, recent studies regarding MCAT element-dependent transcription of the myocardin gene and the smooth muscle alpha-actin gene in muscle provide evidence for the transcriptional diversity among distinct cell types and subtypes. This article summarizes the role of MCAT elements and the TEF-1 family of transcription factors in muscle development and disease, and reviews recent progress in our understanding of the transcriptional regulatory mechanisms involved in MCAT element-dependent muscle-specific gene expression.
Yoshida
Tadashi
T
Department of Molecular Physiology and Biological Physics, University of Virginia, MR5 Room 1226, 415 Lane Road, Charlottesville, Virginia 22908, USA. ty2c@virginia.edu
D000818:Animals; D004268:DNA-Binding Proteins / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006331:Heart Diseases / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D020071:Interspersed Repetitive Sequences / Q000502:physiology*; D051379:Mice; D032342:Muscle Cells / Q000502:physiology*; D018006:Myogenic Regulatory Factors; D009687:Nuclear Proteins / Q000502:physiology*; D000091262:TEA Domain Transcription Factors; D014157:Transcription Factors / Q000502:physiology*
D004268:DNA-Binding Proteins; D018006:Myogenic Regulatory Factors; D009687:Nuclear Proteins; D000091262:TEA Domain Transcription Factors; C057182:TEAD1 protein, human; D014157:Transcription Factors