Download MendeleyAn Atomic Model of the Interferon-beta Enhanceosome.
Panne, D., Maniatis, T., Harrison, S.C.(2007) Cell 129: 1111-1123
- PubMed: 17574024
- DOI: https://doi.org/10.1016/j.cell.2007.05.019
- Primary Citation of Related Structures:
2O61, 2O6G - PubMed 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.
Organizational 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.
