A promoter ISRE and dual 5' YY1 motifs control IFN-gamma induction of the IRG-47 G-protein gene.

The IRG-47 gene is the prototype for a new family of genes encoding guanine nucleotide binding proteins (G-proteins) which are selectively induced in different cell lineages in response to activation signals. The IRG-47 gene is rapidly and transiently induced by interferon-gamma (IFN-gamma) in cells of the B lymphocyte lineage and in stromal cells and fibroblasts. Here we report features controlling the uninduced and IFN-gamma-induced expression of the IRG-47 gene. The minimal IFN-gamma-inducible IRG-47 gene promoter is 96 bp long and contains a TATA box and an ISRE motif with an internal IRF-1/IRF-2 motif. Mutation of the ISRE motif abolishes IFN-gamma induction by the minimal promoter. Constitutively expressed IRF-2 and IFN-gamma-induced IRF-1 factors specifically bind to the wild-type, but not the mutated ISRE motif. An upstream region containing two tandemly repeated YY1 motifs represses the expression of the IRG-47 promoter in uninduced cells and determines the magnitude of IRG-47 promoter activity in IFN-gamma-induced cells. The IRG-47 minimal promoter has the same functional features and organization as the IFN-gamma-inducible promoters of the unrelated murine GBP G-protein multigene family.