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Molecular and Cellular Biology, October 2004, p. 8519-8528, Vol. 24, No. 19
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.19.8519-8528.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

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

Jiyeon Oh,1,{dagger} Zhigao Wang,1,{dagger} Da-Zhi Wang,1,2,{dagger} Ching-Ling Lien,1 Weibing Xing,2 and Eric N. Olson1*

Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas,1 Carolina Cardiovascular Biology Center, Department of Cell and Developmental Biology, University of North Carolina, Chapel Hill, North Carolina2

Received 15 July 2003/ Returned for modification 26 August 2003/ Accepted 16 June 2004

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.

* Corresponding author. Mailing address: Department of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Blvd., Dallas, TX 75390-9148. Phone: (214) 648-1187. Fax: (214) 648-1187. E-mail: eolson{at}hamon.swmed.edu.

{dagger} J.O., Z.W., and D.-Z.W. contributed equally.

Molecular and Cellular Biology, October 2004, p. 8519-8528, Vol. 24, No. 19
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.19.8519-8528.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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