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(Circulation Research. 2003;92:824.)
© 2003 American Heart Association, Inc.

Editorials

Decisions, Decisions ... SRF Coactivators and Smooth Muscle Myogenesis

Mark W. Majesky

From the Carolina Cardiovascular Biology Center, Departments of Medicine and Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC.

Correspondence to Mark W. Majesky, PhD, Carolina Cardiovascular Biology Center, 5109 Neurosciences Research Building, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599. E-mail mmajesky@med.unc.edu

Key Words: smooth muscle cells • differentiation • transcription • signaling pathways

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Smooth muscle-restricted gene transcription depends on a highly conserved cis-regulatory element termed a CArG box [CC(A/T)₆GG]. The CArG box binds serum response factor (SRF), an evolutionarily conserved MADS (MDM1, agamous, deficiens, SRF) domain-containing protein that is required for specification of smooth, cardiac, and skeletal muscle lineages from early mesoderm.¹ SRF is a multifunctional protein that not only binds DNA but also provides docking surfaces within the conserved core MADS domain for interaction with a wide variety of accessory cofactors. Most, but not all, smooth muscle cell (SMC) marker genes examined to date require SRF interactions with pairs of CArG-like elements that often contain single G/C substitutions in the AT-rich core region. However, SRF-CArG interactions alone are not sufficient to produce the diversity of smooth muscle subtypes found within the vascular system. A report by Yoshida et al in this issue of Circulation Research confirms and extends previous work by Wang et al,^2,3 Chen et al,⁴ and Du et al,⁵ suggesting that myocardin is a potent SRF-dependent coactivator for smooth muscle differentiation.⁶

Control of SRF-Dependent Transcription by Accessory Cofactors

SRF-CArG box interactions confer context-dependent and signal-responsive control of muscle-specific gene transcription (Figure). This is accomplished at multiple levels of regulation including control of SRF expression, cytoplasmic to nuclear translocation, alternative splicing, and posttranslational modifications of SRF itself. Perhaps the most important mechanism for control of CArG box-dependent transcription is the physical association of SRF with various cell-restricted and/or signal-dependent accessory factors that confer coactivator or corepressor activity via ternary complex formation. This feature of . . . [Full Text of this Article]

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