Published online before print October 13, 2005, doi: 10.1161/01.RES.0000190670.92879.7d
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Submitted on April 25, 2005
Revised on September 29, 2005
Accepted on September 30, 2005
Bone Morphogenetic Protein Signaling Modulates Myocardin Transactivation of Cardiac Genes
Thomas E. Callis ;
From the Department of Cell and Developmental Biology, Carolina Cardiovascular Biology Center, University of North Carolina, Chapel Hill.
* To whom correspondence should be addressed. E-mail: dawang{at}med.unc.edu.
Bone morphogenetic proteins (BMPs) play important roles in cardiovascular development. However, how BMP-signaling pathways regulate cardiac gene expression is less clear. We have previously identified myocardin as a cardiac and smooth muscle-specific transcriptional cofactor for serum response factor (SRF). Myocardin potently activates target gene expression by tethering with SRF bound to SRF-responsive elements, the CArG box. Here, we show that Smad1, an effector of the BMP-signaling pathway, synergistically activates myocardin-dependent cardiac gene expression. Interestingly, the CArG box is necessary and sufficient to mediate such synergy, whereas no obvious Smad-binding element appears to be involved. Consistent with their functional interaction, we find that myocardin and Smad1 proteins interact directly. Furthermore, myocardin protein levels were dramatically increased by BMP-2 treatment in cardiomyocytes. These findings suggest myocardin participates in a BMP signaling-dependent cardiac gene transcriptional program.
Key words: myocardin • serum response factor • bone morphogenetic protein • Smad • cardiac gene expression
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