INTERFERON-GAMMA-INDUCED TRANSCRIPTION OF THE MURINE ISGF3-GAMMA (P48) GENE IS MEDIATED BY NOVEL FACTORS

In this investigation, we show that the gene encoding p48, a subunit o f transcription factor ISGF3, is transcriptionally induced by interfer on gamma (IFN-gamma). We have identified a novel IFN-gamma-activated r esponse element in the p48 gene promoter. This motif, notated as gamma -activated transcriptional element (GATE), has no significant resembla nce to either pIRE (palindromic IFN-response element) or GAS (the IFN- gamma-activated sequence) but has partial homology to ISRE (IFN-stimul ated response element). When fused to a neutral promoter, GATE, a 24-b p element, induced the expression of reporter genes following IFN-gamm a treatment. In murine RAW cells, two IFN-gamma-inducible factors (GIF ) bind to GATE. finding of these factors to GATE is inhibited by cyclo heximide and staurosporine. Although p48 gene induction is dependent o n STAT1 and JAK1, activated STAT1 does not bind to GATE. Thus, GIFs ap pear to be novel trans-acting factors in the IFN-signaling pathway.