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

141 Citations (Scopus)

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

Fingerprint

HMGA1a Protein
Interferons
Transcription
Proteins
Nucleoproteins
Viruses
Virus Diseases
Transcriptional Activation
DNA
Genes
Chemical activation

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

The role of HMG I(Y) in the assembly and function of the IFN-β enhanceosome. / Yie, Junming; Merika, Menie; Munshi, Nikhil; Chen, Guoying; Thanos, Dimitris.

In: EMBO Journal, Vol. 18, No. 11, 01.06.1999, p. 3074-3089.

Research output: Contribution to journalArticle

Yie, Junming ; Merika, Menie ; Munshi, Nikhil ; Chen, Guoying ; Thanos, Dimitris. / The role of HMG I(Y) in the assembly and function of the IFN-β enhanceosome. In: EMBO Journal. 1999 ; Vol. 18, No. 11. pp. 3074-3089.
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