More Estrogen, More Active

Science Signaling  23 Dec 2008:
Vol. 1, Issue 51, pp. ec440
DOI: 10.1126/scisignal.151ec440

Follicle-stimulating hormone (FSH) is released from the pituitary and controls function of the ovaries through binding to its heterotrimeric guanine nucleotide–binding protein (G protein)–coupled receptor. In the ovaries, FSH promotes synthesis of estrogen. Kouzo-Fujita et al. describe evidence that FSH also acts to promote transcriptional regulation by the estrogen receptor β (ERβ). In a human granulosa tumor cell line, stimulation of FSH receptors led to increased transcription of ERβ target genes as detected with luciferase reporters. The authors searched for proteins that interacted with epitope-tagged ERβ and discovered GIOT-4 (gonadotropin-inducible ovarian transcription factor-4). Expression of GIOT-4 mRNA and protein was increased in response to FSH. Coimmunoprecipitation experiments showed that GIOT-4 also interacted with the Swi/Snf chromatin remodeling complex. Chromatin immunoprecipitation experiments showed that this interaction was associated with FSH-induced demethylation of histone H3K9 and increased acetylation of histone H4. These modifications were diminished after depletion of ERβ or GIOT-4 with RNAi. Thus the authors conclude that GIOT-4 is a transcriptional coactivator for ERβ that mediates enhanced estrogen signaling in response to the gonadotropin FSH.

M. Kouzu-Fujita, Y. Mezaki, S. Sawatsubashi, T. Matsumoto, I. Yamaoka, T. Yano, Y. Taketani, H. Kitagawa, S. Kato, Coactivation of estrogen receptor β by gonadotropin-induced cofactor GIOT-4. Mol. Cell. Biol. 29, 83–92 (2009). [PubMed]