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J. Biol. Chem., Vol. 280, Issue 9, 7786-7792, March 4, 2005

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Recruitment of the Androgen Receptor via Serum Response Factor Facilitates Expression of a Myogenic Gene^*

Spiros Vlahopoulos, Warren E. Zimmer||, Guido Jenster**, Narasimhaswamy S. Belaguli, Steven P. Balk, Albert O. Brinkmann, Rainer B. Lanz, Vassilis C. Zoumpourlis, and Robert J. Schwartz¶

From the Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, the ^||Department of Cell Biology and Neuroscience, University of South Alabama, Mobile, Alabama 36688, the ^**Department of Urology, Erasmus MC, P. O. Box 1738, 3000 DR Rotterdam, The Netherlands, the Cancer Biology Program, Hematology-Oncology Division, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, the Department of Reproduction & Development, Erasmus MC, The Netherlands, and the Unit of Biomedical Applications, Institute of Biological Research and Biotechnology, Hellenic Research Foundation, 48 Vasileos Constantinou Avenue, Athens 11635, Greece

Androgen receptor (AR) induced precocious myogenesis in culture and myogenic specified gene activity. Increased levels of AR expression in replicating C2C12 myoblasts stimulated fusion into post-differentiated multinucleated myotubes and the appearance of skeletal -actin transcripts, even in the absence of ligand. Furthermore, AR activated the skeletal -actin promoter, which lacks GRE sites, in co-transfected C2C12 cells. AR co-activation of the skeletal -actin promoter required co-expressed full-length serum response factor (SRF). In vitro, AR associated with SRF and was recruited by SRF to a -actin promoter SRF binding site. Our data suggest that AR is capable of activating myogenic genes devoid of consensus AR binding sites via its recruitment by the myogenic enriched transcription factor, SRF.

Received for publication, December 13, 2004

^* This work was supported by National Institutes of Health Grants R01 HL50422 and P01 HL49953 (to R. J. S.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^¶ To whom correspondence should be addressed: Inst. of Biosciences and Technology, The Texas A&M University System Health Science Center, 2121 W. Holcombe Blvd., Houston, TX 77030. Tel.: 713-677-7710; E-mail: rschwartz{at}ibt.tamhsc.edu.

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