Estrogen Receptor (ER) β Modulates ERα-Mediated Transcriptional Activation by Altering the Recruitment of c-Fos and c-Jun to Estrogen-Responsive Promoters

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Abstract
In this study, an estrogen receptor (ER) α-expressing T47D cell line containing an inducible tet-off FLAG-ERβ was used to examine the influence of ERβ on ERα activity. Real-time PCR analysis of mRNA levels of two well-studied estrogen-responsive genes, pS2 and progesterone receptor (PR), showed that the expression levels of both genes were reduced in the presence of ERβ. Chromatin immunoprecipitation assays showed that the 17β-estradiol (E2)-induced recruitment patterns to the pS2 and PR promoters were similar for both ERα and ERβ. ERβ expression did not significantly influence the kinetic recruitment profile of ERα to the pS2 promoter, but it was evident that ERα occupancy at the PR promoter was reduced. The E2-induced recruitment of c-Fos to a 12-O-tetradecanoylphorbol-13-acetate response element site in the PR promoter was significantly reduced in the presence of ERβ, whereas only a slight reduction in the recruitment of c-Fos to the pS2 promoter was observed. ERβ expression resulted in a significant reduction in the E2-induced expression of c-Fos mRNA. The recruitment pattern of c-Jun was also altered by ERβ, although the expression levels of c-Jun were not. Expression of ERβ caused a further 30–50% decrease of the E2-induced reduction in ERα protein after 3 h of E2 treatment, showing that ERβ influences ERα protein levels. The altered recruitment of the activating protein-1 complex, combined with the reduction in ERα protein levels, may partly explain the antagonistic effect of ERβ on ERα-mediated transcription.

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