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Molecular and Cellular Biology, January 2005, p. 364-376, Vol. 25, No. 1
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.1.364-376.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Modulation of Smooth Muscle Gene Expression by Association of Histone Acetyltransferases and Deacetylases with Myocardin

Dongsun Cao,1,{dagger} Zhigao Wang,2,{dagger} Chun-Li Zhang,2,{dagger},{ddagger} Jiyeon Oh,2 Weibing Xing,1 Shijie Li,2 James A. Richardson,3 Da-Zhi Wang,1,2* and Eric N. Olson2*

Departments of Molecular Biology,2 Pathology, University of Texas Southwestern Medical Center, Dallas, Texas,3 Carolina Cardiovascular Biology Center, Department of Cell and Developmental Biology, University of North Carolina, Chapel Hill, North Carolina1

Received 10 May 2004/ Returned for modification 1 July 2004/ Accepted 29 September 2004

Differentiation of smooth muscle cells is accompanied by the transcriptional activation of an array of muscle-specific genes controlled by serum response factor (SRF). Myocardin is a cardiac and smooth muscle-specific expressed transcriptional coactivator of SRF and is sufficient and necessary for smooth muscle gene expression. Here, we show that myocardin induces the acetylation of nucleosomal histones surrounding SRF-binding sites in the control regions of smooth muscle genes. The promyogenic activity of myocardin is enhanced by p300, a histone acetyltransferase that associates with the transcription activation domain of myocardin. Conversely, class II histone deacetylases interact with a domain of myocardin distinct from the p300-binding domain and suppress smooth muscle gene activation by myocardin. These findings point to myocardin as a nexus for positive and negative regulation of smooth muscle gene expression by changes in chromatin acetylation.

* Corresponding author. Mailing address: Department of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Blvd., Dallas, TX 75390-9148. Phone for Eric N. Olson: (214) 648-1187. Fax: (214) 648-1196. E-mail: eolson{at}hamon.swmed.edu. Phone for Da-Zhi Wang: (919) 843-4590. Fax: (919) 966-6012. E-mail: dawang{at}med.unc.edu.

{dagger} D.C., Z.W., and C.-L.Z. contributed equally to this work.

{ddagger} Present address: Salk Institute for Biological Studies, La Jolla, CA 92037.

Molecular and Cellular Biology, January 2005, p. 364-376, Vol. 25, No. 1
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.1.364-376.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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