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Author Notes:

Correspondence: Paula M. Vertino, Winship Cancer Institute, Emory University School of Medicine, 1365-C Clifton Rd., NE, Rm. C-4086, Atlanta, GA 30322; Tel.: 404-778-3119; Fax: 404-778-5530; E-mail: pvertin@emory.edu

Acknowledgments: We thank Dr. Paul Wade for materials and advice, Dr. Xing Zhang for technical and conceptual advice and members of the Vertino and Cheng laboratories for helpful discussions and support.

We also thank Drs. Myles Brown, Michael Wang, Xue-Yuan Dong, Jin-Tang Dong and Iannis Talianidis for plasmid constructs.

Subjects:

Research Funding:

This work was supported in part by National Institutes of Health grants 2RO1 CA077337 (PMV), 2RO1 GM068680 (XC) and P50 AG025688 (JP), an American Cancer Society Research Scholar grant RSG-02-144-01 (PMV), and funds from the Burris Foundation (KS) and the Georgia Research Alliance (XC).

Regulation of Estrogen Receptor Alpha by the SET7 lysine methyltransferase

Tools:

Journal Title:

Molecular Cell

Volume:

Volume 30, Number 3

Publisher:

, Pages 336-347

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Summary Estrogen receptor α (ER) is a ligand-dependent transcription factor. Upon binding estrogen, ER recruits coactivator complexes with histone acetyltransferase or methyltransferase activities to activate downstream target genes. In addition to histones, coactivators can modify ER itself and other proteins in the transactivation complex. Here, we show that ER is directly methylated at lysine 302 (K302) by the SET7 methyltransferase. SET7-mediated methylation stabilizes ER and is necessary for the efficient recruitment of ER to its target genes, and their transactivation. The SET7-ER complex structure reveals the molecular basis for ER peptide recognition and predicts that modifications or mutations of nearby residues would affect K302 methylation. Indeed, a breast cancer-associated mutation at K303 (K303R) alters methylation at K302 in vitro and in vivo. These findings raise the possibility that generation, recognition, and removal of modifications within the ER hinge region generates “ER modification cassettes” that yield distinct patterns for signaling downstream events.

Copyright information:

© 2008 Elsevier Inc. Published by Elsevier Inc.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported License (http://creativecommons.org/licenses/by-nc-nd/3.0/).

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