Abstract
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.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Animals
-
Atrial Natriuretic Factor / genetics
-
Binding Sites
-
Bone Morphogenetic Protein 2
-
Bone Morphogenetic Protein Receptors, Type I / physiology
-
Bone Morphogenetic Proteins / pharmacology
-
Bone Morphogenetic Proteins / physiology*
-
COS Cells
-
Chlorocebus aethiops
-
Gene Expression Regulation*
-
Myocardium / metabolism*
-
Myocytes, Cardiac / metabolism
-
Nuclear Proteins / physiology*
-
Promoter Regions, Genetic
-
Response Elements / physiology
-
Serum Response Factor / physiology
-
Signal Transduction / physiology*
-
Smad1 Protein / physiology*
-
Trans-Activators / physiology*
-
Transcriptional Activation*
-
Transforming Growth Factor beta / pharmacology*
Substances
-
Bmp2 protein, mouse
-
Bone Morphogenetic Protein 2
-
Bone Morphogenetic Proteins
-
Nuclear Proteins
-
Serum Response Factor
-
Smad1 Protein
-
Smad1 protein, mouse
-
Trans-Activators
-
Transforming Growth Factor beta
-
myocardin
-
Atrial Natriuretic Factor
-
Bmpr1a protein, mouse
-
Bone Morphogenetic Protein Receptors, Type I