Home LiteratureArticle Details
PMID: 17574024 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

An atomic model of the interferon-beta enhanceosome.

Cell ·Vol. 129 ·No. 6 ·2007-06-15 ·Pages 1111-23

Panne D, Maniatis T, Harrison SC

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.

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
Chemicals
Chromatin Interferon Regulatory Factor-3 Interferon Regulatory Factor-7 NF-kappa B Recombinant Fusion Proteins Interferon-beta
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Panne Daniel
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.
Maniatis Tom
Harrison Stephen C
References (60)
60 references, click to expand
  1. Construction, expression, purification and functional analysis of recombinant NFkappaB p50/p65 heterodimer.
    Protein Eng. 1999 May;12(5):423-8 PMID: 10360983
  2. Structure and function of the interferon-beta enhanceosome.
    Cold Spring Harb Symp Quant Biol. 1998;63:609-20 PMID: 10384326
  3. Crystal structure of an IRF-DNA complex reveals novel DNA recognition and cooperative binding to a tandem repeat of core sequences.
    EMBO J. 1999 Sep 15;18(18):5028-41 PMID: 10487755
  4. Interferon regulatory factors: the next generation.
    Gene. 1999 Sep 3;237(1):1-14 PMID: 10524230
  5. Mechanism by which the IFN-beta enhanceosome activates transcription.
    Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):13108-13 PMID: 10557281
  6. Regulation of DNA binding by Rel/NF-kappaB transcription factors: structural views.
    Oncogene. 1999 Nov 22;18(49):6845-52 PMID: 10602460
  7. Evidence for stabilizing selection in a eukaryotic enhancer element.
    Nature. 2000 Feb 3;403(6769):564-7 PMID: 10676967
  8. Assembly of a functional beta interferon enhanceosome is dependent on ATF-2-c-jun heterodimer orientation.
    Mol Cell Biol. 2000 Jul;20(13):4814-25 PMID: 10848607
  9. Selective DNA binding and association with the CREB binding protein coactivator contribute to differential activation of alpha/beta interferon genes by interferon regulatory factors 3 and 7.
    Mol Cell Biol. 2000 Sep;20(17):6342-53 PMID: 10938111
  10. Distinct and essential roles of transcription factors IRF-3 and IRF-7 in response to viruses for IFN-alpha/beta gene induction.
    Immunity. 2000 Oct;13(4):539-48 PMID: 11070172
  11. Ordered recruitment of chromatin modifying and general transcription factors to the IFN-beta promoter.
    Cell. 2000 Nov 10;103(4):667-78 PMID: 11106736
  12. The IFN-beta enhancer: a paradigm for understanding activation and repression of inducible gene expression.
    Cold Spring Harb Symp Quant Biol. 1999;64:149-59 PMID: 11232280
  13. Enhanceosomes.
    Curr Opin Genet Dev. 2001 Apr;11(2):205-8 PMID: 11250145
  14. HMG1 and 2: architectural DNA-binding proteins.
    Biochem Soc Trans. 2001 Aug;29(Pt 4):395-401 PMID: 11497996
  15. Gene regulation. A paradigm for precision.
    Science. 2001 Aug 10;293(5532):1054-5 PMID: 11498564
  16. Coordination of a transcriptional switch by HMGI(Y) acetylation.
    Science. 2001 Aug 10;293(5532):1133-6 PMID: 11498590
  17. Nucleosome sliding via TBP DNA binding in vivo.
    Cell. 2001 Sep 21;106(6):685-96 PMID: 11572775
  18. A small domain of CBP/p300 binds diverse proteins: solution structure and functional studies.
    Mol Cell. 2001 Sep;8(3):581-90 PMID: 11583620
  19. Preferential binding sites for interferon regulatory factors 3 and 7 involved in interferon-A gene transcription.
    J Mol Biol. 2002 Mar 8;316(5):1009-22 PMID: 11884139
  20. The x-ray crystal structure of the NF-kappa B p50.p65 heterodimer bound to the interferon beta -kappa B site.
    J Biol Chem. 2002 Jul 5;277(27):24694-700 PMID: 11970948
  21. The kappa B DNA sequence from the HIV long terminal repeat functions as an allosteric regulator of HIV transcription.
    J Biol Chem. 2002 Jul 5;277(27):24701-8 PMID: 11970949
  22. Structure of NF-kappaB p50/p65 heterodimer bound to the PRDII DNA element from the interferon-beta promoter.
    Structure. 2002 Mar;10(3):383-91 PMID: 12005436
  23. Crystal structure of PU.1/IRF-4/DNA ternary complex.
    Mol Cell. 2002 Nov;10(5):1097-105 PMID: 12453417
  24. 3DNA: a software package for the analysis, rebuilding and visualization of three-dimensional nucleic acid structures.
    Nucleic Acids Res. 2003 Sep 1;31(17):5108-21 PMID: 12930962
  25. The high mobility group protein HMG I(Y) is required for NF-kappa B-dependent virus induction of the human IFN-beta gene.
    Cell. 1992 Nov 27;71(5):777-89 PMID: 1330326
  26. An ATF/CREB binding site is required for virus induction of the human interferon beta gene [corrected].
    Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2150-4 PMID: 1532252
  27. Crystal structure of ATF-2/c-Jun and IRF-3 bound to the interferon-beta enhancer.
    EMBO J. 2004 Nov 10;23(22):4384-93 PMID: 15510218
  28. Coot: model-building tools for molecular graphics.
    Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2126-32 PMID: 15572765
  29. Transcriptional enhancers: Intelligent enhanceosomes or flexible billboards?
    J Cell Biochem. 2005 Apr 1;94(5):890-8 PMID: 15696541
  30. Functional evolution of a cis-regulatory module.
    PLoS Biol. 2005 Apr;3(4):e93 PMID: 15757364
  31. IRF-7 is the master regulator of type-I interferon-dependent immune responses.
    Nature. 2005 Apr 7;434(7034):772-7 PMID: 15800576
  32. Crystal structure of IRF-3 in complex with CBP.
    Structure. 2005 Sep;13(9):1269-77 PMID: 16154084
  33. Improved methods for building protein models in electron density maps and the location of errors in these models.
    Acta Crystallogr A. 1991 Mar 1;47 ( Pt 2):110-9 PMID: 2025413
  34. Transcriptional regulation of a pair-rule stripe in Drosophila.
    Genes Dev. 1991 May;5(5):827-39 PMID: 2026328
  35. The definition of generalized helicoidal parameters and of axis curvature for irregular nucleic acids.
    J Biomol Struct Dyn. 1988 Aug;6(1):63-91 PMID: 2482765
  36. Processing of X-ray diffraction data collected in oscillation mode.
    Methods Enzymol. 1997;276:307-26 PMID: 27754618
  37. Evidence for a nuclear factor(s), IRF-1, mediating induction and silencing properties to human IFN-beta gene regulatory elements.
    EMBO J. 1988 Nov;7(11):3397-405 PMID: 2850164
  38. Overlapping positive and negative regulatory domains of the human beta-interferon gene.
    Proc Natl Acad Sci U S A. 1988 Mar;85(5):1447-51 PMID: 3422743
  39. Structure of NF-kappa B p50 homodimer bound to a kappa B site.
    Nature. 1995 Jan 26;373(6512):303-10 PMID: 7530332
  40. Transcription factor ATF2 regulation by the JNK signal transduction pathway.
    Science. 1995 Jan 20;267(5196):389-93 PMID: 7824938
  41. Structure of the NF-kappa B p50 homodimer bound to DNA.
    Nature. 1995 Jan 26;373(6512):311-7 PMID: 7830764
  42. The high mobility group protein HMG I(Y) is an essential structural component of a virus-inducible enhancer complex.
    Cold Spring Harb Symp Quant Biol. 1993;58:73-81 PMID: 7956090
  43. Stimulation of c-Jun activity by CBP: c-Jun residues Ser63/73 are required for CBP induced stimulation in vivo and CBP binding in vitro.
    Oncogene. 1995 Dec 21;11(12):2509-14 PMID: 8545107
  44. Virus induction of human IFN beta gene expression requires the assembly of an enhanceosome.
    Cell. 1995 Dec 29;83(7):1091-100 PMID: 8548797
  45. Reversal of intrinsic DNA bends in the IFN beta gene enhancer by transcription factors and the architectural protein HMG I(Y).
    Cell. 1995 Dec 29;83(7):1101-11 PMID: 8548798
  46. Oct-1 POU domain-DNA interactions: cooperative binding of isolated subdomains and effects of covalent linkage.
    Genes Dev. 1996 Jan 1;10(1):27-36 PMID: 8557192
  47. The solution structure of an HMG-I(Y)-DNA complex defines a new architectural minor groove binding motif.
    Nat Struct Biol. 1997 Aug;4(8):657-65 PMID: 9253416
  48. Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain.
    Cell. 1997 Aug 22;90(4):595-606 PMID: 9288740
  49. NUCPLOT: a program to generate schematic diagrams of protein-nucleic acid interactions.
    Nucleic Acids Res. 1997 Dec 15;25(24):4940-5 PMID: 9396800
  50. Structure of IRF-1 with bound DNA reveals determinants of interferon regulation.
    Nature. 1998 Jan 1;391(6662):103-6 PMID: 9422515
  51. p300 and ATF-2 are components of the DRF complex, which regulates retinoic acid- and E1A-mediated transcription of the c-jun gene in F9 cells.
    Genes Dev. 1998 Jan 15;12(2):233-45 PMID: 9436983
  52. Crystal structure of p50/p65 heterodimer of transcription factor NF-kappaB bound to DNA.
    Nature. 1998 Jan 22;391(6665):410-3 PMID: 9450761
  53. Structure of the DNA-binding domains from NFAT, Fos and Jun bound specifically to DNA.
    Nature. 1998 Mar 5;392(6671):42-8 PMID: 9510247
  54. Virus-dependent phosphorylation of the IRF-3 transcription factor regulates nuclear translocation, transactivation potential, and proteasome-mediated degradation.
    Mol Cell Biol. 1998 May;18(5):2986-96 PMID: 9566918
  55. Recruitment of CBP/p300 by the IFN beta enhanceosome is required for synergistic activation of transcription.
    Mol Cell. 1998 Jan;1(2):277-87 PMID: 9659924
  56. Virus infection induces the assembly of coordinately activated transcription factors on the IFN-beta enhancer in vivo.
    Mol Cell. 1998 Mar;1(4):507-18 PMID: 9660935
  57. Phosphorylation of NF-kappa B p65 by PKA stimulates transcriptional activity by promoting a novel bivalent interaction with the coactivator CBP/p300.
    Mol Cell. 1998 Apr;1(5):661-71 PMID: 9660950
  58. Crystallography & NMR system: A new software suite for macromolecular structure determination.
    Acta Crystallogr D Biol Crystallogr. 1998 Sep 1;54(Pt 5):905-21 PMID: 9757107
  59. Differential viral induction of distinct interferon-alpha genes by positive feedback through interferon regulatory factor-7.
    EMBO J. 1998 Nov 16;17(22):6660-9 PMID: 9822609
  60. Positive feedback regulation of type I IFN genes by the IFN-inducible transcription factor IRF-7.
    FEBS Lett. 1998 Dec 11;441(1):106-10 PMID: 9877175
Article Info
Journal
Cell
Abbr.
Cell
ISSN
0092-8674
DOI
10.1016/j.cell.2007.05.019
Published
2007-06-15
Pages
1111-23
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC2020837
Subset
IM
Grants
NIAID NIH HHS · R01 AI020642 · United States
NIAID NIH HHS · R01 AI020642-23 · United States
NIAID NIH HHS · R01AI020642 · United States
Databases
PDB
2O6G, 2O6I
External Links
PubMed source DOI: 10.1016/j.cell.2007.05.019 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2