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Myocardin is a master regulator of smooth muscle gene expression

Zhigao Wang1, Da-Zhi Wang, G C Teg Pipes

  • 1Department of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390-9148, USA.

Proceedings of the National Academy of Sciences of the United States of America
|May 21, 2003
PubMed

Insights

Myocardin, a protein specific to cardiac and smooth muscle, acts as a master regulator. It works with serum response factor (SRF) to control smooth muscle gene expression, even in non-muscle cells.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cardiovascular Biology

Background:

  • Smooth muscle-specific gene expression relies on serum response factor (SRF) binding sites.
  • SRF alone cannot explain the specificity of smooth muscle gene expression due to its widespread presence.
  • A key regulatory mechanism for smooth muscle genes remains unidentified.

Purpose of the Study:

  • To identify the coactivator responsible for smooth muscle-specific gene expression.
  • To elucidate the role of myocardin in regulating smooth muscle genes.
  • To understand how SRF achieves cell-type specificity in gene regulation.

Main Methods:

  • Analysis of smooth muscle gene control regions for SRF binding sites.
  • Investigating the function of myocardin as a transcriptional coactivator of SRF.
  • Assessing the impact of myocardin homodimerization on transcriptional activity.
  • Utilizing nonmuscle cell types to test the specificity of SRF-myocardin interactions.

Main Results:

  • Myocardin, a cardiac and smooth muscle-specific coactivator, activates SRF-mediated transcription of smooth muscle genes.
  • Myocardin can confer smooth muscle gene expression specificity in nonmuscle cells through association with SRF.
  • Myocardin homodimerization is essential for maximal transcriptional activity.
  • SRF-myocardin complexes exhibit cooperative activation of smooth muscle genes.

Conclusions:

  • Myocardin is identified as a master regulator of smooth muscle gene expression.
  • Myocardin explains how SRF directs smooth muscle-specific gene expression.
  • The interaction between SRF and myocardin provides a mechanism for precise gene regulation in muscle tissues.

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