An Atomic Model of the Interferon-β Enhanceosome
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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.
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Virtually every nucleotide of the interferon beta enhancer is evolutionarily conserved, likely because eight transcription factors cooperate to form a composite surface that recognises the entire sequence as one effective binding site.
“Virtually every nucleotide of the interferon beta enhancer is evolutionarily conserved; this is likely because the eight TFs cooperate to form a composite surface that recognises the entire sequence of the enhancer as one effective binding site [88, 89].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [89]
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- Authors
- Panne, D., Maniatis, T., & Harrison, S. C.
- Affiliations
- Howard Hughes Medical Institute (US)
- Harvard University (US)
- Corresponding author
- Harrison, Stephen C.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2007-06
- Volume
- 129
- Issue
- 6
- Pages
- 1111-1123
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC2020837
- OpenAlex
- W2098188064
- Cited by
- 625
- References
- 6
- Citations by year
- 2026: 27 · 2025: 33 · 2024: 25 · 2023: 27 · 2022: 29 · 2021: 36 · 2020: 30 · 2019: 29 · 2018: 35 · 2017: 20 · 2016: 29 · 2015: 30 · 2014: 35 · 2013: 32 · 2012: 33
- FWCI
- 16.62
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- Agência Nacional de Energia Elétrica
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (R01AI020642)
- Argonne National Laboratory
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- interferon-beta, enhanceosome, IRF3, IRF7, NF-κB, transcriptional activation, crystal structure, cooperative DNA binding, DNA conformational change, CBP, protein-DNA complex
- MeSH terms
- Base Sequence, Chromatin, Crystallization, Humans, Models, Biological, Molecular Conformation, Molecular Sequence Data, Nucleic Acid Conformation, Recombinant Fusion Proteins, Transcriptional Activation, NF-kappa B, Interferon-beta, Crystallography, X-Ray, Interferon Regulatory Factor-3, Interferon Regulatory Factor-7
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