Abstract
We show that the IRF-2 oncoprotein represses virus-induced IFN-beta gene transcription via a novel mechanism. Virus infection induces recruitment of IRF-2 to some of the endogenous IFN-beta enhancers as part of the enhanceosome. Enhanceosomes bearing IRF-2 cannot activate transcription, due to the presence of a domain in IRF-2 that prevents enhanceosome-dependent recruitment of the CBP-Pol II holoenzyme complex. As a consequence, IRF-2 incorporation into enhanceosomes restricts the number of IFN-beta promoters directing transcription. Remarkably, deletion of the IRF-2 gene increases IFN-beta expression by expanding the number of cells capable of inducing IFN-beta gene transcription in response to virus infection.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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COS Cells
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Cell Nucleus / metabolism
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Chlorocebus aethiops
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Chromatin / physiology
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Enhancer Elements, Genetic*
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Gene Expression Regulation*
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Genes, Reporter
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Green Fluorescent Proteins
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HeLa Cells
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Humans
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Interferon Regulatory Factor-2
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Interferon-beta / genetics*
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Luminescent Proteins / genetics
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Mice
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Mice, Knockout
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Promoter Regions, Genetic
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RNA, Antisense / genetics
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Recombinant Fusion Proteins / metabolism
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Repressor Proteins / genetics
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Repressor Proteins / metabolism
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Transcription Factors*
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Transcription, Genetic*
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Transfection
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Viruses / immunology*
Substances
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Chromatin
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DNA-Binding Proteins
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IRF2 protein, human
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Interferon Regulatory Factor-2
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Irf2 protein, mouse
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Luminescent Proteins
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RNA, Antisense
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Recombinant Fusion Proteins
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Repressor Proteins
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Transcription Factors
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Green Fluorescent Proteins
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Interferon-beta