Target gene-specific modulation of myocardin activity by GATA transcription factors.
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.
Oh
Jiyeon
J
Department of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Blvd., Dallas, TX 75390-9148, USA.
Wang
Zhigao
Z
Wang
Da-Zhi
DZ
Lien
Ching-Ling
CL
Xing
Weibing
W
Olson
Eric N
EN
D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D050991:GATA4 Transcription Factor; D005786:Gene Expression Regulation / Q000502:physiology*; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D014981:Xenopus; D029867:Xenopus Proteins / Q000096:biosynthesis / Q000235:genetics; D000099251:Myocardin
D004268:DNA-Binding Proteins; D050991:GATA4 Transcription Factor; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D029867:Xenopus Proteins; D000099251:Myocardin; C494751:GATA4 protein, Xenopus; C092720:NKX2-5 protein, Xenopus