Interferon γ-induced transcription of the murine ISGF3γ (p48) gene is mediated by novel factors

In this investigation, we show that the gene encoding p48, a subunit of transcription factor ISGF3, is transcriptionally induced by interferon γ (IFN-γ). We have identified a novel IFN-γ-activated response element in the p48 gene promoter. This motif, notated as gamma-activated transcriptional element (GATE), has no significant resemblance to either pIRE (palindromic IFN-response element) or GAS (the IFN-γ-activated sequence) but has partial homology to ISRE (IFN-stimulated response element). When fused to a neutral promoter, GATE, a 24-bp element, induced the expression of reporter genes following IFN-γ treatment. In murine RAW cells, two IFN-gamma-inducible factors (GIF) bind to GATE. Binding of these factors to GATE is inhibited by cycloheximide and staurosporine. Although p48 gene induction is dependent on STAT1 and JAK1, activated STAT1 does not bind to GATE. Thus, GIFs appear to be novel trans-acting factors in the IFN-signaling pathway.