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  • Title: Distinct activation of murine interferon-alpha promoter region by IRF-1/ISFG-2 and virus infection.
    Author: Au WC, Raj NB, Pine R, Pitha PM.
    Journal: Nucleic Acids Res; 1992 Jun 11; 20(11):2877-84. PubMed ID: 1614874.
    Abstract:
    Virus infection in mouse L929 cells activates expression of interferon-alpha 4 (IFN-alpha 4), but not IFN-alpha 6. The integrity of a symmetrical sequence, GTAAAGAAAGT (alpha F1 site); (-103 to -93), present in the 35 nucleotide (nt) long inducible element (IE) (-109 to -75) of the alpha 4 promoter region is essential for the virus-induced expression. In the present study, we have shown that the interferon regulatory factor 1 (IRF-1) can induce expression of both IFN-alpha 4 and -alpha 6 in a transient expression assay. Virus infection cooperates with IRF-1 and further enhances transcription from the alpha 4 promoter, but inhibits the IRF-1-mediated expression from the alpha 6 promoter. The virus-mediated induction is determined by both IRF-1 and alpha F1 sites, while activation by IRF-1 in a cotransfection assay is not greatly influenced by the alpha F1 sequence. The activation of IFN-alpha gene promoters by IRF-1 was limited to the transient expression assay. The integrated alpha 4 promoter or the endogenous IFN-alpha genes could not be induced by transfection with IRF-1 expressing plasmid and IRF-1 did not up-regulate expression of the endogenous IRF-1 gene. However, expression of IRF-1 alone was sufficient to up-regulate the expression of two IFN stimulated genes, 2',5' oligoadenylate synthetase (OAS) and interferon stimulated (ISG)-15 gene. These results suggest that induction of IFN-alpha gene expression by virus infection requires cooperation between IRF-1 and another factor(s) that binds to the alpha F1 sequence.
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