Gene repression by coactivator repulsion

We show that the IRF-2 oncoprotein represses virus-induced IFN-beta gene tr anscription via a novel mechanism. Virus infection induces recruitment of I RF-2 to some of the endogenous IFN-beta enhancers as part of the enhanceoso me. Enhanceosomes bearing IRF-2 cannot activate transcription, due to the p resence of a domain in IRF-2 that prevents enhanceosome-dependent recruitme nt of the CBP-Pol II holoenzyme complex. As a consequence, IRF-2 incorporat ion into enhanceosomes restricts the number of IFN-beta promoters directing transcription. Remarkably, deletion of the IRF-2 gene increases IFN-beta e xpression by expanding the number of cells capable of inducing IFN-beta gen e transcription in response to virus infection.