tailieunhanh - Báo cáo khoa học: Mechanism for transcriptional synergy between interferon regulatory factor (IRF)-3 and IRF-7 in activation of the interferon-b gene promoter

Theinterferon-bpromoter has been studied extensively as a model system for combinatorial transcriptional regulation. Invirus-infectedcells the transcription factorsATF-2, c-Jun, interferon regulatory factor (IRF)-3, IRF-7andNF-jB, and the coactivators p300/CBP play critical roles in the activa-tion of this and other promoters. It remains unclear, how-ever, why most other combinations of AP-1, IRF and Rel proteins fail to activate theinterferon-bgene. Here we have explored how different IRFs may cooperate with other fac-tors to activate transcription | Eur. J. Biochem. 271 3693-3703 2004 FEBS 2004 doi Mechanism for transcriptional synergy between interferon regulatory factor IRF -3 and IRF-7 in activation of the interferon-b gene promoter Hongmei Yang1 Gang Ma1 Charles H. Lin2 I Melissa Orr1 and Marc G. Wathelet1 1Department of Molecular and Cellular Physiology University of Cincinnati College of Medicine Cincinnati OH USA department of Molecular and Cellular Biology Harvard University Cambridge MA USA The interferon-b promoter has been studied extensively as a model system for combinatorial transcriptional regulation. In virus-infected cells the transcription factors ATF-2 c-Jun interferon regulatory factor IRF -3 IRF-7 and NF-kB and the coactivators p300 CBP play critical roles in the activation of this and other promoters. It remains unclear however why most other combinations of AP-1 IRF and Rel proteins fail to activate the interferon-b gene. Here we have explored how different IRFs may cooperate with other factors to activate transcription. First we showed in undifferentiated embryonic carcinoma cells that ectopic expression of either IRF-3 or IRF-7 but not IRF-1 was sufficient to allow virus-dependent activation of the interferon-b promoter. Moreover the activity of IRF-3 and IRF-7 was strongly affected by promoter context with IRF-7 preferentially being recruited to the natural interferon-b promoter. We fully reconstituted activation of this promoter in insect cells. Maximal synergy required IRF-3 and IRF-7 but not IRF-1 and was strongly dependent on the presence of p300 CBP even when these coactivators only modestly affected the activity of each factor by itself. These results suggest that specificity in activation of the interferon-b gene depends on a unique promoter context and on the role played by coactivators as architectural factors. Keywords coactivator interferon IRF synergy virus. Specificity in transcriptional regulation is thought to derive in part from the .