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.
Gilly
M
M
Department of Microbiology and Immunology, School of Medicine, University of California, Los Angeles 90095, USA.
Damore
M A
MA
Wall
R
R
D000818:Animals; D001483:Base Sequence; D004247:DNA; D004268:DNA-Binding Proteins / Q000378:metabolism; D050981:Erythroid-Specific DNA-Binding Factors; D019204:GTP-Binding Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D007371:Interferon-gamma / Q000494:pharmacology*; D051379:Mice; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012097:Repressor Proteins; D014157:Transcription Factors / Q000378:metabolism; D050986:YY1 Transcription Factor
D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; C102949:IFI47 protein, mouse; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; C494258:Irf1 protein, mouse; C494230:Irf2 protein, mouse; D010750:Phosphoproteins; D012097:Repressor Proteins; D014157:Transcription Factors; D050986:YY1 Transcription Factor; C494699:Yy1 protein, mouse; D007371:Interferon-gamma; D004247:DNA; D019204:GTP-Binding Proteins