Identification of a phorbol ester-responsive element in the interferon-gamma receptor 1 chain gene.
Human monocytic leukemia THP-1 cells differentiate into macrophage-like cells when treated with 12-O-tetradecanoylphorbol-13-acetate (TPA). During this process, interferon-gamma (IFN-gamma)-inducible expression of human leukocyte antigen-DR alpha is markedly enhanced. The enhancement of human leukocyte antigen-DR alpha expression is at least due to the TPA-dependent induction of the IFN-gamma receptor 1 chain and IFN-gamma receptor 2 chain genes. Here we have studied the mechanism of TPA-induced up-regulation of the IFN-gamma receptor 1 chain gene. Reporter gene analyses of 5'-deletion constructs of the IFN-gamma receptor 1 gene (IFNGR1) promoter indicated that the critical region for control of transcription and the TPA-responsive element (TRE) were present in the -128 to -109 base pair (bp) region. We confirmed that this region of the IFNGR1 promoter was responsive to TPA-induced signals by using a reporter construct whose promoter consisted of the -128 to -109 bp fragment and the minimal herpes simplex virus thymidine kinase promoter. Moreover, a supershift assay indicated that Sp1 bound to this TRE in TPA-treated THP-1 cells. These results suggest that in TPA-treated cells the binding of Sp1 to the TRE of the IFNGR1 promoter causes the up-regulation of this gene.
Sakamoto
S
S
Laboratory of Molecular Biology, Medical Research Center, Kochi Medical School, Okoh, Nankoku, Kochi 783-8505, Japan.
Taniguchi
T
T
D001483:Base Sequence; D002273:Carcinogens / Q000494:pharmacology*; D002478:Cells, Cultured; D004247:DNA / Q000032:analysis; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000187:drug effects; D017471:Receptors, Interferon / Q000187:drug effects / Q000235:genetics*; D050794:STAT1 Transcription Factor; D012694:Serine / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D015534:Trans-Activators / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism; D000096743:Interferon gamma Receptor
D002273:Carcinogens; D004247:DNA; D004268:DNA-Binding Proteins; D007371:Interferon-gamma; D009687:Nuclear Proteins; D017471:Receptors, Interferon; D050794:STAT1 Transcription Factor; D012694:Serine; D013755:Tetradecanoylphorbol Acetate; D015534:Trans-Activators; D014443:Tyrosine; D000096743:Interferon gamma Receptor; C494079:STAT1 protein, human