Target Gene-Specific Modulation of Myocardin Activity by GATA Transcription Factors

Abstract

Myocardin is a transcriptional coactivator that regulates cardiac and smooth muscle gene expression by associating with serum response factor. We show that GATA transcription factors can either stimulate or suppress the transcriptional activity of myocardin, depending on the target gene. Modulation of myocardin activity by GATA4 is mediated by the physical interaction of myocardin with the DNA binding domain of GATA4 but does not require binding of GATA4 to DNA. Paradoxically, the transcription activation domain of GATA4 is dispensable for the stimulatory effect of GATA4 on myocardin activity but is required for repression of myocardin activity. The ability of GATA transcription factors to modulate myocardin activity provides a potential mechanism for fine tuning the expression of serum response factor target genes in a gene-specific manner.

We thank Bruce Markham and Robert Schwartz for reagents and Yibin Wang for assistance with adenoviruses. We are also grateful to Alisha Tizenor for assistance with graphics and Jennifer Page for editorial assistance.

This work was supported by grants from the National Institutes of Health, the Donald W. Reynolds Clinical Cardiovascular Research Center, and the Robert A. Welch Foundation to E.N.O. D.Z.W. was supported by the Muscular Dystrophy Association and a start-up fund from the University of North Carolina.