An atomic model of the interferon-beta enhanceosome

Cell. 2007 Jun 15;129(6):1111-23. doi: 10.1016/j.cell.2007.05.019.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Base Sequence
  • Chromatin / chemistry
  • Crystallization
  • Crystallography, X-Ray
  • Humans
  • Interferon Regulatory Factor-3 / metabolism
  • Interferon Regulatory Factor-7 / metabolism
  • Interferon-beta / metabolism*
  • Models, Biological
  • Molecular Conformation
  • Molecular Sequence Data
  • NF-kappa B / metabolism
  • Nucleic Acid Conformation
  • Recombinant Fusion Proteins / chemistry
  • Transcriptional Activation


  • Chromatin
  • Interferon Regulatory Factor-3
  • Interferon Regulatory Factor-7
  • NF-kappa B
  • Recombinant Fusion Proteins
  • Interferon-beta

Associated data

  • PDB/2O6G
  • PDB/2O6I