THE GENOMIC STRUCTURE OF THE MURINE ICSBP GENE REVEALS THE PRESENCE OF THE GAMMA INTERFERON-RESPONSIVE ELEMENT, TO WHICH AN ISGF3-ALPHA SUBUNIT (OR SIMILAR) MOLECULE BINDS

ICSBP, a member of the interferon regulatory factor family, is express ed predominantly in lymphoid tissues and is induced by gamma interfero n (IFN-gamma). We have studied the genomic organization of the murine ICSBP gene and its 5' upstream region. The murine ICSBP gene (Icsbp) i s present as a single copy on chromosome 8 and consists of nine exons. Transcription initiates at two juxtaposed sites downstream from the T ATA and CAAT boxes and produces two species of ICSBP mRNA (3.0 and 1.7 kb), presumably by differential usage of poly(A)+ signals. A sequence from -175 to -155 was identified to be an IFN response region that co nferred IFN-gamma induction upon a heterologous promoter in lymphoid c ell line ELA. This region includes a motif, TTCNNGGAA, designated the palindromic IFN response element (pIRE), to which an IFN-gamma-inducib le, cycloheximide-sensitive factor(s) binds. A similar palindromic mot if was found in the upstream region of the murine IRF-1 gene, the IFN- gamma activation site of the guanylate-binding protein gene and the IF N-gamma-responsive region of the Fc receptor type I gene, all of which competed with the pIRE for factor binding in gel mobility shift assay s. We show that the pIRE binding factor reacts with the antibody again st the 91-kDa subunit of ISGF3alpha recently shown to bind to the IFN- gamma activation site. These results suggest that this factor is relat ed to the IFN-gamma activation factor and contains the 91-kDa subunit of ISGF3alpha. Taken together, pIRE represents an IRE that is distinct from the classical IFN-stimulated response element and that is capabl e of conferring IFN-gamma induction through the binding of the 91-kDa ISGF3alpha subunit (or an antigenically similar molecule).