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- W2078763947 abstract "We describe the molecular features of the interferon (IFN)-γ-mediated transcription of the human intercellular adhesion molecule (ICAM-1) gene. We identified putative IFN-γ-activated sites (GAS) distributed throughout a large segment of the ICAM-1 promoter (4.0 kb region). Using computer-assisted search, these sequences were similar to potential IFN-γ responsive elements that have a core sequence 5′-TTNCNNNAA-3′. In this report we show that in the ICAM-1 promoter a GAS site is located at −115 from the translation initiation site, and binds with strong affinity to IFN-γ-activated Signal Transducers and Activators of Transcription (STAT1) homodimers. The same sequence is responsible for the IFN-γ-mediated transcription of the ICAM-1 gene. Moreover, we present evidence that a more distal GAS element that maps at −2787 from the translation initiation site, binds IFN-γ-activated STAT1 dimers with lower affinity. Multimeric copies of such GAS sequence inserted into a tkCAT minimal promoter can drive transcription, demonstrating that the −2787 bp GAS element has an independent functional activity upon binding of IFN-γ-activated STAT1 proteins as documented by in vitro binding assays. Furthermore, using recombinant ICAM-CAT mutants, we show that, in vivo, the −2787 GAS, but not a mutagenized −2787 GAS site, when coupled to the more proximal −115 GAS element, has an additive effect in enhancing the IFN-γ-mediated transcription of ICAM-1 promoter. Nevertheless, using a recombinant construct bearing the wild type −2787 GAS element and a mutagenized −115 GAS element, we could not detect any transcription after transfection of U937 recipient cells, suggesting that the −2787 bp GAS element is not sufficient as such for gene activation, but can cooperate with its cognate proximal sequence to give full function to the ICAM-1 promoter during the IFN-γ response. Taken together these data provide evidence that two GAS sites are required for the full potential activity in the mechanism of ICAM-1 gene activation by IFN-γ." @default.
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- W2078763947 date "1998-12-15" @default.
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- W2078763947 title "Two gamma-interferon-activation sites (GAS) on the promoter of the human intercellular adhesion molecule (ICAM-1) gene are required for induction of transcription by IFN-gamma" @default.
- W2078763947 doi "https://doi.org/10.1046/j.1432-1327.1998.2580968.x" @default.
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