Recruitment of CBP/p300 by the IFN beta enhanceosome is required for synergistic activation of transcription.
Transcriptional activation of the IFN beta gene in response to virus infection requires the assembly of an enhanceosome, consisting of the transcriptional activators NF-kappa B, IRF1, ATF2/c-Jun, and the architectural protein HMG I(Y). The level of transcription generated by all of these activators is greater than the sum of the levels generated by individual factors, a phenomenon designated transcriptional synergy. We demonstrate that this synergy, in the context of the enhanceosome, requires a new protein-protein interaction domain in the p65 subunit of NF-kappa B. Transcriptional synergy requires recruitment of the CBP/p300 coactivator to the enhanceosome, via a new activating surface assembled from the novel p65 domain and the activation domains of all of the activators. Deletion, substitution, or rearrangement of any one of the activation domains in the context of the enhanceosome decreases both recruitment of CBP and transcriptional synergy.
Merika
M
M
Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032, USA.
Williams
A J
AJ
Chen
G
G
Collins
T
T
Thanos
D
D
D051698:Activating Transcription Factor 2; D000818:Animals; D001665:Binding Sites / Q000502:physiology; D019556:COS Cells; D050882:CREB-Binding Protein; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004742:Enhancer Elements, Genetic / Q000502:physiology*; D015967:Gene Expression Regulation, Viral; D051548:Histone Acetyltransferases; D050856:Interferon Regulatory Factor-1; D016899:Interferon-beta / Q000235:genetics*; D016350:Leucine Zippers / Q000235:genetics; D016328:NF-kappa B / Q000737:chemistry / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D056921:Nuclear Receptor Coactivator 3; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051996:Transcription Factor RelA; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation / Q000502:physiology*; D014162:Transfection
D051698:Activating Transcription Factor 2; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D050856:Interferon Regulatory Factor-1; D016328:NF-kappa B; D009687:Nuclear Proteins; D010750:Phosphoproteins; D016755:Proto-Oncogene Proteins c-jun; D015534:Trans-Activators; D051996:Transcription Factor RelA; D014157:Transcription Factors; D016899:Interferon-beta; D050882:CREB-Binding Protein; D051548:Histone Acetyltransferases; D056921:Nuclear Receptor Coactivator 3