Combinatorial control of smooth muscle-specific gene expression.
Alterations in the differentiated state of vascular smooth muscle cells (SMCs) are known to play a key role in vascular diseases, yet the mechanisms controlling SMC differentiation are still poorly understand. In this review, we discuss our present knowledge of control of SMC differentiation at the transcriptional level, pointing out some common themes, important paradigms, and unresolved issues in SMC-specific gene regulation. We focus primarily on the serum response factor-CArG box-dependent pathway, because it has been shown to play a critical role in regulation of multiple SMC marker genes. However, we also highlight several other important regulatory elements, such as a transforming growth factor beta control element, E-boxes, and MCAT motifs. We present evidence in support of the notion that SMC-specific gene regulation is not controlled by a few SMC-specific transcription factors but rather by complex combinatorial interactions between multiple general and tissue-specific proteins. Finally, we discuss the implications of chromatin remodeling on SMC differentiation.
Kumar
Meena S
MS
Department of Molecular Physiology and Biological Physics, University of Virginia, 415 Lane Rd, MR5 Room 1220, PO Box 801394, Charlottesville, VA 22908, USA. gko@virginia.edu
Owens
Gary K
GK
D000818:Animals; D015415:Biomarkers; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D002843:Chromatin / Q000235:genetics / Q000648:ultrastructure; D005786:Gene Expression Regulation / Q000187:drug effects; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D027602:Serum Response Element; D026362:Serum Response Factor / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology; D014158:Transcription, Genetic / Q000187:drug effects
D015415:Biomarkers; D002843:Chromatin; D006133:Growth Substances; D026362:Serum Response Factor; D014157:Transcription Factors