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

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, DNA, DNA Footprinting, DNA-Binding Proteins, Dimerization, Enhancer Elements, Genetic, HMGA1a Protein, Hela Cells, High Mobility Group Proteins, Humans, Interferon Regulatory Factor-1, Interferon-beta, Models, Genetic, Mutation, NF-kappa B, Phosphoproteins, Protein Binding, Protein Biosynthesis, Proto-Oncogene Proteins c-jun, Recombinant Fusion Proteins, Repetitive Sequences, Amino Acid, Transcription Factors, Transcription, Genetic
EMBO J.
Date: Jun. 01, 1999
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