Gilly M, Damore M A, Wall R
Department of Microbiology and Immunology, School of Medicine, University of California, Los Angeles 90095, USA.
Gene. 1996 Nov 14;179(2):237-44. doi: 10.1016/s0378-1119(96)00366-6.
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.
IRG - 47基因是编码鸟嘌呤核苷酸结合蛋白（G蛋白）的新基因家族的原型，这些蛋白在不同细胞谱系中响应激活信号而被选择性诱导。在B淋巴细胞谱系的细胞以及基质细胞和成纤维细胞中，IRG - 47基因可被γ干扰素（IFN - γ）快速且短暂地诱导。在此我们报告了控制IRG - 47基因未诱导表达和IFN - γ诱导表达的特征。最小的IFN - γ可诱导的IRG - 47基因启动子长96 bp，包含一个TATA盒和一个带有内部IRF - 1/IRF - 2基序的ISRE基序。ISRE基序的突变消除了最小启动子对IFN - γ的诱导作用。组成性表达的IRF - 2和IFN - γ诱导的IRF - 1因子特异性结合野生型而非突变的ISRE基序。一个包含两个串联重复YY1基序的上游区域在未诱导细胞中抑制IRG - 47启动子的表达，并决定IFN - γ诱导细胞中IRG - 47启动子活性的大小。IRG - 47最小启动子具有与不相关的小鼠GBP G蛋白多基因家族的IFN - γ可诱导启动子相同的功能特征和组织形式。
