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PMID: 10357819 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

The EMBO journal ·Vol. 18 ·No. 11 ·1999-06-01 ·Pages 3074-89

Yie J, Merika M, Munshi N, Chen G, Thanos D

Abstract

Transcriptional activation of the virus inducible enhancer of the human interferon-beta (IFN-beta) gene in response to virus infection requires the assembly of an enhanceosome, consisting of the transcriptional activators NF-kappaB, 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-kappaB 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-beta enhanceosome is an unusually stable nucleoprotein structure that can activate transcription at high levels by promoting multiple rounds of reinitiation of transcription.

MeSH Terms
Activating Transcription Factor 2 Allosteric Regulation Cyclic AMP Response Element-Binding Protein/metabolism DNA/genetics,metabolism DNA Footprinting DNA-Binding Proteins/metabolism Dimerization Enhancer Elements, Genetic/genetics HMGA1a Protein HeLa Cells High Mobility Group Proteins/chemistry,genetics,metabolism Humans Interferon Regulatory Factor-1 Interferon-beta/genetics Models, Genetic Mutation NF-kappa B/metabolism Phosphoproteins/metabolism Protein Binding Protein Biosynthesis Proto-Oncogene Proteins c-jun/metabolism Recombinant Fusion Proteins/chemistry,genetics,metabolism Repetitive Sequences, Amino Acid Transcription Factors/chemistry,genetics,metabolism Transcription, Genetic/genetics
Chemicals
ATF2 protein, human Activating Transcription Factor 2 Cyclic AMP Response Element-Binding Protein DNA-Binding Proteins High Mobility Group Proteins IRF1 protein, human Interferon Regulatory Factor-1 NF-kappa B Phosphoproteins Proto-Oncogene Proteins c-jun Recombinant Fusion Proteins Transcription Factors HMGA1a Protein Interferon-beta DNA
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Yie J
Department of Biochemistry and Molecular Biophysics, Columbia University, 630 West 168th Street, New York, NY 10032, USA.
Merika M
Munshi N
Chen G
Thanos D
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/18.11.3074
Published
1999-06-01
Pages
3074-89
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1171389
Subset
IM
Grants
NIGMS NIH HHS · 1RO1GM54605 · United States
NIGMS NIH HHS · 6-T32-GM0767 · United States
External Links
PubMed source DOI: 10.1093/emboj/18.11.3074 PMC Full Text View journal details
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