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J. Biol. Chem., Vol. 276, Issue 40, 37237-37241, October 5, 2001

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Identification of a Phorbol Ester-responsive Element in the Interferon- Receptor 1 Chain Gene^*

Shuji Sakamoto and Taketoshi Taniguchi^§

From the Laboratory of Molecular Biology, Medical Research Center, Kochi Medical School, Okoh, Nankoku, Kochi 783-8505, Japan

Human monocytic leukemia THP-1 cells differentiate into macrophage-like cells when treated with 12-O-tetradecanoylphorbol-13-acetate (TPA). During this process, interferon- (IFN-)-inducible expression of human leukocyte antigen-DR is markedly enhanced. The enhancement of human leukocyte antigen-DR expression is at least due to the TPA-dependent induction of the IFN- receptor 1 chain and IFN- receptor 2 chain genes. Here we have studied the mechanism of TPA-induced up-regulation of the IFN- receptor 1 chain gene. Reporter gene analyses of 5'-deletion constructs of the IFN- 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.

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