The interferon-tau (IFN-tau) are Type I IFN produced in trophectoderm of ruminants. They prevent the regression of the corpus luteum when a viable embryo is present in the uterus. The IFN-tau possess properties in common with other IFN, but their function in maternal recognition of pregnancy likely depends upon uncharacterized signal transduction pathways. IFN-tau have potential value as therapeutic agents as they reportedly exhibit broad cross-species reactivity and low cytotoxicity. Their genes are also not inducible by virus, and their expression is limited to trophectoderm prior to trophoblast attachment. Our goal is to determine how the IFN-tau differ from their close relatives in the way they initiate signaling and in their transcriptional control. There are nine aims: 1) To determine whether a recombinant IFN-tau is superior to an IFN-alpha and an IFN-omega as an antiluteolytic agent by comparing the three in their abilities to extend estrous cycle length in ewes. 2) To purify and characterize a membrane-associated protein from sheep endometrium that becomes cross-linked to IFN-tau but not to IFN- alpha. 3) To use the yeast two-hybrid screen to identify endometrial proteins that bind the cytoplasmic domain of the Type I receptor subunits. 4) To identify proteins that become rapidly phosphorylated in endometrium in response to IFN-tau, but not to IFN-alpha. 5) To compare the expression of Ets2 and Oct3/4, two transcription factors implicated in IFN-tau gene expression, in developing bovine embryos. 6) To identify co-activators that operate in association with Ets2. 7) By using the yeast single- hybrid screen, identify additional factors that transactivate IFN-tau genes. 8) To determine the mechanism whereby Oct3/4 inhibits the activation of IFN-tau genes by Ets2. 9) To utilize a recently developed bovine trophectoderm cell line to study trophectoderm function and IFN-tau expression. Together these studies will provide information on roles for IFN in non- pathogenic processes and insight into how trophectoderm differentiates during early embryonic development.
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