The role of HMG I(Y) in the assembly and function of the IFN-β enhanceosome

Junming Yie, Menie Merika, Nikhil Munshi, Guoying Chen, Dimitris Thanos

Research output: Contribution to journalArticle

144 Scopus citations

Abstract

Transcriptional activation of the virus inducible enhancer of the human interferon-β (IFN-β) gene in response to virus infection requires the assembly of an enhanceosome, consisting of the transcriptional activators NF-κB, ATF-2/c-Jun, IRFs and the architectural protein of the mammalian high mobility group I(Y) [HMG I(Y)]. Here, we demonstrate that the first step in enhanceosome assembly, i.e. HMG I(Y)-dependent recruitment of NF-κB and ATF-2/c-Jun to the enhancer, is facilitated by discrete regions of HMG I and is mediated by allosteric changes induced in the DNA by HMG I(Y) and not by protein-protein interactions between HMG I(Y) and these proteins. However, we show that completion of the enhanceosome assembly process requires protein-protein interactions between HMG I(Y) and the activators. Finally, we demonstrate that once assembled, the IFN-β enhanceosome is an unusually stable nucleoprotein structure that can activate transcription at high levels by promoting multiple rounds of reinitiation of transcription.

Original languageEnglish (US)
Pages (from-to)3074-3089
Number of pages16
JournalEMBO Journal
Volume18
Issue number11
DOIs
StatePublished - Jun 1 1999

Keywords

  • Enhanceosome assembly
  • HMG I(Y)
  • IFN-β
  • Protein-protein interaction
  • Transcriptional activator

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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