Cloning of the ovine estrogen receptor-alpha promoter and functional regulation by ovine interferon-tau

Interferon-tau (IFN tau), the ruminant pregnancy recognition signal, inhibi ts transcription of the estrogen receptor alpha (ER alpha) gene in the endo metrial lumenal epithelium of the sheep uterus, thereby abrogating producti on of luteolytic PGF(2 alpha) pulses. The effects of IFN tau are mediated i n part by IFN-stimulated response elements (ISREs) and IFN regulatory facto r elements (IRFEs). The promoter/enhancer region of the ovine ER alpha gene was cloned, sequenced, and predicted to contain four IRFEs and one ISRE. E lectrophoretic mobility shift assays indicated that the -2110 IRFE bound on ly IRF-1, whereas the -1877 IRFE and the -1284 ISRE were functional in bind ing IRF-1 and IRF-2. IFN tau inhibited transcriptional activity of the 2.7- kb ovine ER alpha promoter in transfection assays using ovine lumenal epith elium cells. Analyses of sequential 5 ' -deletion mutants of the ovine ER a lpha promoter indicated that the effects of IFN tau may be mediated by IRFE s as well as other elements. Overexpression of ovine IRF-2, but not IRF-1, inhibited transcriptional activity of several regions of the ovine ER alpha promoter containing an IRFE or an ISRE as well as some, but not all, regio ns lacking these elements.