title: An atomic model of the interferon-beta enhanceosome.
abstract: Transcriptional activation of the interferon-beta (IFN-beta) gene requires assembly of an enhanceosome containing ATF-2/c-Jun, IRF-3/IRF-7, and NFkappaB. 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 NFkappaB, 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.
authors.affiliation: The Jack and Eileen Connors Structural Biology Laboratory, Harvard Medical School, Department of Biological Chemistry and Molecular Pharmacology, Howard Hughes Medical Institute, 250 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Panne
authors.forename: Tom
authors.initials: T
authors.lastname: Maniatis
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Harrison
mesh_terms: D001483:Base Sequence; D002843:Chromatin / Q000737:chemistry; D003460:Crystallization; D018360:Crystallography, X-Ray; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D050839:Interferon Regulatory Factor-7 / Q000378:metabolism; D016899:Interferon-beta / Q000378:metabolism*; D008954:Models, Biological; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D009690:Nucleic Acid Conformation; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D015533:Transcriptional Activation
chemical_list: D002843:Chromatin; D050838:Interferon Regulatory Factor-3; D050839:Interferon Regulatory Factor-7; D016328:NF-kappa B; D011993:Recombinant Fusion Proteins; D016899:Interferon-beta