Open AccessCoactivation of Estrogen Receptor β by Gonadotropin-Induced Cofactor GIOT-4
Author(s) -
Madoka Kouzu-Fujita,
Yoshihiro Mezaki,
Shun Sawatsubashi,
Takahiro Μatsumoto,
Ikuko Yamaoka,
Tetsu Yano,
Yuji Taketani,
Hirochika Kitagawa,
Shigeaki Kato
Publication year - 2009
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.00884-08
Subject(s) - biology , estrogen receptor , transcription factor , coactivator , medicine , endocrinology , estrogen receptor alpha , estrogen receptor beta , estrogen , downregulation and upregulation , granulosa cell , microbiology and biotechnology , ovary , gene , genetics , cancer , breast cancer
Estrogen exerts its diverse effects through two subtypes of estrogen receptors (ER), ERα 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.