Myocardin, an early cardiac and smooth muscle cell lineage marker, is a transcriptional co-activator of serum response factor (Srf), which regulates the expression of many myogenic genes. But what regulates myocardin expression? On , Eric Olson's team reports that a combination of Mef2, Tead and Foxo transcription factors regulates myocardin expression during cardiovascular development. By examining the expression of a lacZreporter gene linked to various non-coding regions of the gene in transgenic mice, the researchers identified a 10 kb fragment that recapitulates the expression pattern of myocardin during cardiogenesis. They then homed in on a 350 bp enhancer region within this fragment, the activity of which requires the combined action of Mef2 and Foxo in cardiomyocytes, plus Tead in smooth muscle cells. Other results indicate that, unlike most myogenic genes,myocardin expression does not depend on Srf. Instead, myocardin activates its own enhancer via Mef2. This suggests that a unique positive-feedback loop regulates smooth- and cardiac-muscle-specific transcription during cardiovascular development.
