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Molecular and Cellular Biology, November 2006, p. 7846-7857, Vol. 26, No. 21
0270-7306/06/$08.00+0     doi:10.1128/MCB.00568-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Signaling within a Coactivator Complex: Methylation of SRC-3/AIB1 Is a Molecular Switch for Complex Disassembly{triangledown}

Qin Feng, Ping Yi, Jiemin Wong, and Bert W. O'Malley*

Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030

Received 31 March 2006/ Returned for modification 17 May 2006/ Accepted 14 August 2006

Recent studies indicate that steroid receptor-mediated transcriptional initiation is a cyclical process involving multiple rounds of coactivator assembly and disassembly. Steroid receptor coactivator 3 (SRC-3) coactivator phosphorylation has been shown to regulate coactivator complex assembly, but the mechanisms by which coactivator disassembly is triggered are not well understood. In this study, we provide in vitro and in vivo evidence that members of the SRC coactivator family serve as substrates for the enzymatic coactivator coactivator-associated arginine methyltransferase 1 (CARM1). Methylation of SRC-3 was localized to an arginine in its CARM1 binding region and correlated with decreased estrogen receptor alpha-mediated transcription, as seen with both cell-based and in vitro transcription assays. Consistent with this finding, we demonstrated that methylation promotes dissociation of the SRC-3/CARM1 coactivator complex. Methylation of SRC-3 is regulated by estrogen signaling in MCF7 cells and serves as a molecular switch for disassembly of the SRC-3 transcriptional coactivator complex. We propose that CARM1 is a dual-function coactivator, as it not only activates transcription by modifying core histone tails but also terminates hormone signaling by disassembly of the coactivator complex.

* Corresponding author. Mailing address: Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. Phone: (713) 798-6205. Fax: (713) 798-5599. E-mail: berto{at}bcm.tmc.edu.

{triangledown} Published ahead of print on 21 August 2006.

Molecular and Cellular Biology, November 2006, p. 7846-7857, Vol. 26, No. 21
0270-7306/06/$08.00+0     doi:10.1128/MCB.00568-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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