Coactivation of estrogen receptor beta by gonadotropin-induced cofactor GIOT-4.
Estrogen exerts its diverse effects through two subtypes of estrogen receptors (ER), ERalpha and ERbeta. Each subtype has its own distinct function and expression pattern in its target tissues. Little, however, is known about the transcriptional regulatory mechanism of ERbeta in the major ERbeta-expressing tissues. Using biochemical methods, we identified and described a novel ERbeta coactivator. This protein, designated GIOT-4, was biochemically purified from 293F cells. It coactivated ERbeta 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 ERbeta as an ER subtype-specific physical bridging factor and induced subsequent histone modifications in the ERbeta target gene promoters in a human ovarian granulosa cell line (KGN). Indeed, two ERbeta-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 ERbeta-mediated transcription in the ovary.
Kouzu-Fujita
Madoka
M
Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
Mezaki
Yoshihiro
Y
Sawatsubashi
Shun
S
Matsumoto
Takahiro
T
Yamaoka
Ikuko
I
Yano
Tetsu
T
Taketani
Yuji
Y
Kitagawa
Hirochika
H
Kato
Shigeaki
S
D000818:Animals; D002460:Cell Line; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005640:Follicle Stimulating Hormone / Q000031:analogs & derivatives / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006064:Gonadotropins, Equine / Q000494:pharmacology; D006657:Histones / Q000378:metabolism; D006801:Humans; D051379:Mice; D008954:Models, Biological; D038081:Organogenesis / Q000187:drug effects; D006080:Ovarian Follicle / Q000187:drug effects / Q000196:embryology; D011485:Protein Binding / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D020218:Response Elements; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects
D002868:Chromosomal Proteins, Non-Histone; D047629:Estrogen Receptor beta; D006064:Gonadotropins, Equine; D006657:Histones; C445179:SWI-SNF-B chromatin-remodeling complex; D014157:Transcription Factors; C534290:ZNF14 protein, human; D005640:Follicle Stimulating Hormone; D017868:Cyclic AMP-Dependent Protein Kinases