The transcriptional code of human IFN-beta gene expression

Abstract

Activation of interferon-beta transcription is a highly ordered process beginning with the delivery of NF-kappaB to the IFN-beta enhancer through a process involving stochastic interchromosomal interactions between the IFN-beta enhancer and specialized Alu elements. NF-kappaB delivery is followed by the binding of ATF-2/c-Jun and IRF proteins in a highly cooperative fashion. The assembled "enhanceosome" then recruits PCAF/GCN5 which acetylates the histone tails of the adjacent nucleosomes. The transcriptional coactivator CBP, which binds in a complex with the RNA polymerase II holoenzyme is recruited by the enhanceosome replacing PCAF/GCN5. Next, SWI/SNF, which is part of the holoenzyme complex, induces a conformational change in a nucleosome positioned over the transcriptional start site allowing TFIID to bind, which promotes the sliding of this nucleosome to a new downstream position. At this point the full pre-initiation complex is assembled and transcription commences. This detailed picture of the IFN-beta transcription program gathered through years of rigorous studies, now serves as a paradigm for understanding complex transcriptional switches in eukaryotic systems.