Gene repression by coactivator repulsion.
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.
Senger
K
K
Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032, USA.
Merika
M
M
Agalioti
T
T
Yie
J
J
Escalante
C R
CR
Chen
G
G
Aggarwal
A K
AK
Thanos
D
D
D000818:Animals; D019556:COS Cells; D002467:Cell Nucleus / Q000378:metabolism; D002522:Chlorocebus aethiops; D002843:Chromatin / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D006367:HeLa Cells; D006801:Humans; D050836:Interferon Regulatory Factor-2; D016899:Interferon-beta / Q000235:genetics*; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D011401:Promoter Regions, Genetic; D016372:RNA, Antisense / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors; D014158:Transcription, Genetic; D014162:Transfection; D014780:Viruses / Q000276:immunology*
D002843:Chromatin; D004268:DNA-Binding Proteins; C494229:IRF2 protein, human; D050836:Interferon Regulatory Factor-2; C494230:Irf2 protein, mouse; D008164:Luminescent Proteins; D016372:RNA, Antisense; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D049452:Green Fluorescent Proteins; D016899:Interferon-beta