An Atomic Model of the Interferon-[beta] EnhanceosomeCell, Vol. 129, No. 6. (15 June 2007), pp. 1111-1123.
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AbstractSummary Transcriptional activation of the interferon-[beta] (IFN-[beta]) gene requires assembly of an enhanceosome containing ATF-2/c-Jun, IRF-3/IRF-7, and NF[kappa]B. These factors bind cooperatively to the IFN-[beta] enhancer and recruit coactivators and chromatin-remodeling proteins to the IFN-[beta] promoter. We describe here a crystal structure of the DNA-binding domains of IRF-3, IRF-7, and NF[kappa]B, bound to one half of the enhancer, and use a previously described structure of the remaining half to assemble a complete picture of enhanceosome architecture in the vicinity of the DNA. Association of eight proteins with the enhancer creates a continuous surface for recognizing a composite DNA-binding element. Paucity of local protein-protein contacts suggests that cooperative occupancy of the enhancer comes from both binding-induced changes in DNA conformation and interactions with additional components such as CBP. Contacts with virtually every nucleotide pair account for the evolutionary invariance of the enhancer sequence.
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