Bone morphogenetic protein signaling modulates myocardin transactivation of cardiac genes.
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.
Callis
Thomas E
TE
Department of Cell and Developmental Biology, Carolina Cardiovascular Biology Center, University of North Carolina, Chapel Hill, NC, USA.
Cao
Dongsun
D
Wang
Da-Zhi
DZ
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics; D001665:Binding Sites; D055396:Bone Morphogenetic Protein 2; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000502:physiology; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology / Q000502:physiology*; D019556:COS Cells; D002522:Chlorocebus aethiops; D005786:Gene Expression Regulation; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism; D009687:Nuclear Proteins / Q000502:physiology*; D011401:Promoter Regions, Genetic; D020218:Response Elements / Q000502:physiology; D026362:Serum Response Factor / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D051898:Smad1 Protein / Q000502:physiology*; D015534:Trans-Activators / Q000502:physiology*; D015533:Transcriptional Activation; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D000099251:Myocardin
D009320:Atrial Natriuretic Factor; D055396:Bone Morphogenetic Protein 2; D052005:Bone Morphogenetic Protein Receptors, Type I; D019485:Bone Morphogenetic Proteins; D009687:Nuclear Proteins; D026362:Serum Response Factor; D051898:Smad1 Protein; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D000099251:Myocardin; C525719:Bmp2 protein, mouse; C497401:Smad1 protein, mouse; C498212:Bmpr1a protein, mouse