Cloning of the ovine estrogen receptor-alpha promoter and functional regulation by ovine interferon-tau
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Interferon- (IFN), the ruminant pregnancy recognition signal, inhibits transcription of the estrogen receptor (ER) gene in the endometrial lumenal epithelium of the sheep uterus, thereby abrogating production of luteolytic PGF2pulses. The effects of IFN are mediated in part by IFN-stimulated response elements (ISREs) and IFN regulatory factor elements (IRFEs). The promoter/enhancer region of the ovine ER gene was cloned, sequenced, and predicted to contain four IRFEs and one ISRE. Electrophoretic mobility shift assays indicated that the -2110 IRFE bound only IRF-1, whereas the -1877 IRFE and the -1284 ISRE were functional in binding IRF-1 and IRF-2. IFN inhibited transcriptional activity of the 2.7-kb ovine ER promoter in transfection assays using ovine lumenal epithelium cells. Analyses of sequential 5-deletion mutants of the ovine ER promoter indicated that the effects of IFN may be mediated by IRFEs as well as other elements. Overexpression of ovine IRF-2, but not IRF-1, inhibited transcriptional activity of several regions of the ovine ER promoter containing an IRFE or an ISRE as well as some, but not all, regions lacking these elements.