Specific Binding of the ETS-Domain Protein to the Interferon-Stimulated Response Element

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Abstract
Interferon (IFN) activation of genes bearing an IFN-stimulated response element (ISRE) is regulated through binding of IFN-stimulated gene factors (ISGF) to the ISRE found in many IFN-stimulated genes. Using a multimerized human 2-5A synthetase ISRE as probe, we screened λgtll expression libraries for cDNA encoding ISRE-binding activity and isolated a clone for the murine proto-oncogene ets-1. The Ets-1 protein binds to the 2-5 A synthetase ISRE at a site that also binds ISGF3, a multicomponent factor whose ISRE binding correlates with IFN-induced activation of transcription from ISRE-containing promoters. IFN-induced ISGF3 complex formation on the ISRE can be inhibited by specific Ets-1 antibody. Coexpression of Ets-1 represses ISRE-dependent reporter activity, suggesting that one or more members of the Ets protein family may negatively regulate transcriptional activity mediated by the 2-5A synthetase ISRE.