Activation of cardiac gene expression by myocardin, a transcriptional cofactor for serum response factor.
Serum response factor (SRF) regulates transcription of numerous muscle and growth factor-inducible genes. Because SRF is not muscle specific, it has been postulated to activate muscle genes by recruiting myogenic accessory factors. Using a bioinformatics-based screen for unknown cardiac-specific genes, we identified a novel and highly potent transcription factor, named myocardin, that is expressed in cardiac and smooth muscle cells. Myocardin belongs to the SAP domain family of nuclear proteins and activates cardiac muscle promoters by associating with SRF. Expression of a dominant negative mutant of myocardin in Xenopus embryos interferes with myocardial cell differentiation. Myocardin is the founding member of a class of muscle transcription factors and provides a mechanism whereby SRF can convey myogenic activity to cardiac muscle genes.
PubMed ID: 11439182
Article link: Cell.
Grant support: HL63926 NHLBI NIH HHS
Genes referenced: actl6a apcs myocd nkx2-5 srf actc1 tpm1
Article Images: [+] show captions
|Figure 7. Inhibition of Myocardial Gene Expression by Expression of Dominant Negative Myocardin in Xenopus EmbryosXenopus embryos at the 8-cell stage were injected with mRNA encoding the Cδ585 mutant of myocardin and GFP or GFP alone (control) and were assayed for expression of (A) cardiac α-actin, (B) α-tropomyosin, or (C) Nkx2.5 at stage 28 by whole-mount in situ hybridization. (A, e), (B, c), and (C) show ventral views; other panels show lateral views. The dotted line bisects the symmetrical heart-forming region. Arrowheads show the heart on the injected side, which displays a reduced level of expression of cardiac markers. cg, cement gland; h, heart; s, somites|