Cloning of interferon-stimulated gene 17: The promoter and nuclear proteins that regulate transcription

A member of the interferon-stimulated gene (ISG) family encodes a 17-kDa ub iquitin homolog called ISG17 that is induced in the bovine uterine endometr ium by interferon-tau (IFN-tau) during early pregnancy. The bovine (b) ISG1 7 cDNA shares 30% identity with a tandem ubiquitin repeat and 70% identity with human (h) ISG15. The present experiments were designed to sequence the bISG17 gene, compare general structure with the hISG15 gene, and to identi fy transcription factors that were induced by IFN-tau in bovine endometrial (BEND) cells. The promoter of the bISG17 gene was similar to the hISG15 ge ne in placement of a tandem IFN-stimulatory response element (ISRE) at posi tion -90, but unique in the presence of three additional ISREs at positions -123, -332, and -525, IFN-tau (25 nM) induced nuclear proteins in BEND cel ls that interacted with a tandem bISG17 ISRE in electrophoretic mobility sh ift assay (EMSA), IFN-regulatory factor-1 (IRF-1) bound to this ISRE based upon supershift EMSA using antiserum against IRF-1. IFN-tau activated STAT- 1 (signal transducer and activator of transcription-1) and -2 by 0.5 h, and IRF-1 by 2 h in BEND cells. It is concluded that the bISG17 gene is simila r to the hISG15 gene, retains an ISRE that interacts with IRF-1, and is pos sibly induced initially by the STATs and later by IRF-1 in response to IFN- tau during early pregnancy.