on March 6, 2003
Arteriosclerosis, Thrombosis, and Vascular Biology. 2003
Published online before print March 6, 2003, doi: 10.1161/01.ATV.0000065197.07635.BA
Published online before print March 6, 2003, doi: 10.1161/01.ATV.0000065197.07635.BA
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Submitted on December 13, 2002
Accepted on February 14, 2003
Combinatorial Control of Smooth Muscle-Specific Gene Expression
Meenakshi S. Kumar and Gary K. Owens *
From the Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Va.
* To whom correspondence should be addressed. E-mail: gko{at}virginia.edu.
Abstract--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 
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.
Key words: smooth muscle cells • differentiation • transcriptional regulation • serum response factor • CArG box
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