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PubMed · 11090630

Gene repression by coactivator repulsion.

K Senger·M Merika·T Agalioti·J Yie·C R Escalante·G Chen·A K Aggarwal·D Thanos
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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.

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AnimalsCOS CellsCell NucleusChlorocebus aethiopsChromatinDNA-Binding ProteinsEnhancer Elements, GeneticGene Expression RegulationGenes, ReporterGreen Fluorescent ProteinsHeLa CellsHumansInterferon Regulatory Factor-2Interferon-betaLuminescent ProteinsMiceMice, KnockoutPromoter Regions, GeneticRNA, AntisenseRecombinant Fusion ProteinsRepressor ProteinsTranscription FactorsTranscription, GeneticTransfectionVirusesJournal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.

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K Senger, M Merika, T Agalioti, J Yie, C R Escalante, G Chen, A K Aggarwal, D Thanos. 2000. Gene repression by coactivator repulsion.. https://doi.org/10.1016/s1097-2765(05)00081-x

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