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.
Yie
J
J
Department of Biochemistry and Molecular Biophysics, Columbia University, 630 West 168th Street, New York, NY 10032, USA.
Merika
M
M
Munshi
N
N
Chen
G
G
Thanos
D
D
D051698:Activating Transcription Factor 2; D000494:Allosteric Regulation; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000378:metabolism; D018983:DNA Footprinting; D004268:DNA-Binding Proteins / Q000378:metabolism; D019281:Dimerization; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D025741:HMGA1a Protein; D006367:HeLa Cells; D006609:High Mobility Group Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D050856:Interferon Regulatory Factor-1; D016899:Interferon-beta / Q000235:genetics*; D008957:Models, Genetic; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D011485:Protein Binding; D014176:Protein Biosynthesis; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020449:Repetitive Sequences, Amino Acid; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics*
C497105:ATF2 protein, human; D051698:Activating Transcription Factor 2; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D016328:NF-kappa B; D010750:Phosphoproteins; D016755:Proto-Oncogene Proteins c-jun; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D025741:HMGA1a Protein; D016899:Interferon-beta; D004247:DNA