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Molecular and Cellular Biology, January 2009, p. 83-92, Vol. 29, No. 1
0270-7306/09/$08.00+0     doi:10.1128/MCB.00884-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Coactivation of Estrogen Receptor β by Gonadotropin-Induced Cofactor GIOT-4 {triangledown}

Madoka Kouzu-Fujita,1,2 Yoshihiro Mezaki,1 Shun Sawatsubashi,1,3 Takahiro Matsumoto,1,3 Ikuko Yamaoka,1,3 Tetsu Yano,2 Yuji Taketani,2 Hirochika Kitagawa,1 and Shigeaki Kato1,3*

Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-0032, Japan,1 Department of Obstetrics and Gynecology, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0865, Japan,2 ERATO, Japan Science and Technology Agency, Honcho 4-1-8, Kawaguchi, Saitama 332-0012, Japan3

Received 4 June 2008/ Returned for modification 17 July 2008/ Accepted 8 October 2008

Estrogen exerts its diverse effects through two subtypes of estrogen receptors (ER), ER{alpha} and ERβ. Each subtype has its own distinct function and expression pattern in its target tissues. Little, however, is known about the transcriptional regulatory mechanism of ERβ in the major ERβ-expressing tissues. Using biochemical methods, we identified and described a novel ERβ coactivator. This protein, designated GIOT-4, was biochemically purified from 293F cells. It coactivated ERβ in ovarian granulosa cells. GIOT-4 expression was induced by stimulation with follicle-stimulating hormone (FSH). GIOT-4 recruited an SWI/SNF-type complex in a ligand-independent manner to ERβ as an ER subtype-specific physical bridging factor and induced subsequent histone modifications in the ERβ target gene promoters in a human ovarian granulosa cell line (KGN). Indeed, two ERβ-specific target genes were upregulated by FSH at a specific stage of a normal ovulatory cycle in intact mice. These findings imply the presence of a novel regulatory convergence between the gonadotropin signaling cascade and ERβ-mediated transcription in the ovary.


* Corresponding author. Mailing address: Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan. Fax: 81-3-5841-8477. Phone: 81-3-5841-8478. E-mail: uskato{at}mail.ecc.u-tokyo.ac.jp

{triangledown} Published ahead of print on 3 November 2008.


Molecular and Cellular Biology, January 2009, p. 83-92, Vol. 29, No. 1
0270-7306/09/$08.00+0     doi:10.1128/MCB.00884-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.




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