The specificity of innate immune responses is enforced by repression of interferon response elements by NF-κB p50

Science Signaling

Volumn 4, Issue 161, 2011, Pages

  Cheng, Christine S ^a,b   Feldman, Kristyn E ^a   Lee, James ^a   Verma, Shilpi ^c   Huang, De Bin ^a   Huynh, Kim ^a   Chang, Mikyoung ^d   Ponomarenko, Julia V ^e   Sun, Shao Cong ^d   Benedict, Chris A ^c   Ghosh, Gourisankar ^a   Hoffmann, Alexander ^a,b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b University of California San Diego   (United States)

^c LA JOLLA INSTITUTE FOR ALLERGY AND IMMUNOLOGY   (United States)

^d UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^e UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BACTERIAL DNA; BETA INTERFERON; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERFERON; INTERFERON REGULATORY FACTOR; PROTEIN P50; TOLL LIKE RECEPTOR 9;

AMINO ACID SEQUENCE; ANIMAL CELL; ARTICLE; BACTERIAL IMMUNITY; CHEMICAL ANALYSIS; CONTROLLED STUDY; CYTOKINE PRODUCTION; GENE EXPRESSION; GENE TARGETING; GENOME; HUMAN; HUMAN CELL; IMMUNE RESPONSE; INNATE IMMUNITY; MACROPHAGE; MATHEMATICAL MODEL; NONHUMAN; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN BINDING; PROTEIN EXPRESSION; VIRUS INFECTION; ANIMAL; C57BL MOUSE; CELL LINE; DNA PROBE; METABOLISM; MOUSE; NUCLEOTIDE SEQUENCE; PHYSIOLOGY;

BACTERIA (MICROORGANISMS);

ANIMALS; BASE SEQUENCE; CELL LINE; DNA PROBES; HUMANS; IMMUNITY, INNATE; INTERFERONS; MICE; MICE, INBRED C57BL; NF-KAPPA B P50 SUBUNIT;

EID: 79952173562     PISSN: 19450877     EISSN: 19379145     Source Type: Journal    
DOI: 10.1126/scisignal.2001501     Document Type: Article

References (70)

1. O. Takeuchi, S. Akira, Pattern recognition receptors and inflammation. Cell 140, 805-820 (2010).
2. G. J. Nau, J. F. Richmond, A. Schlesinger, E. G. Jennings, E. S. Lander, R. A. Young, Human macrophage activation programs induced by bacterial pathogens. Proc. Natl. Acad. Sci. U.S.A. 99, 1503-1508 (2002).
3. S. Doyle, S. Vaidya, R. O'Connell, H. Dadgostar, P. Dempsey, T. Wu, G. Rao, R. Sun, M. Haberland, R. Modlin, G. Cheng, IRF3 mediates a TLR3/TLR4-specific antiviral gene program. Immunity 17, 251-263 (2002).
4. S. Ogawa, J. Lozach, C. Benner, G. Pascual, R. K. Tangirala, S. Westin, A. Hoffmann, S. Subramaniam, M. David, M. G. Rosenfeld, C. K. Glass, Molecular determinants of crosstalk between nuclear receptors and toll-like receptors. Cell 122, 707-721 (2005).
5. S. L. Foster, D. C. Hargreaves, R. Medzhitov, Gene-specific control of inflammation by TLR-induced chromatin modifications. Nature 447, 972-978 (2007).
6. C. Nathan, Points of control in inflammation. Nature 420, 846-852 (2002).
7. T. Decker, M. Müller, S. Stockinger, The yin and yang of type I interferon activity in bacterial infection. Nat. Rev. Immunol. 5, 675-687 (2005).
8. A. Marshak-Rothstein, Toll-like receptors in systemic autoimmune disease. Nat. Rev. Immunol. 6, 823-835 (2006).
9. J. C. Roach, K. D. Smith, K. L. Strobe, S. M. Nissen, C. D. Haudenschild, D. Zhou, T. J. Vasicek, G. A. Held, G. A. Stolovitzky, L. E. Hood, A. Aderem, Transcription factor expression in lipopolysaccharide-activated peripheral-blood-derived mononuclear cells. Proc. Natl. Acad. Sci. U.S.A. 104, 16245-16250 (2007).
10. S. A. Ramsey, S. L. Klemm, D. E. Zak, K. A. Kennedy, V. Thorsson, B. Li, M. Gilchrist, E. S. Gold, C. D. Johnson, V. Litvak, G. Navarro, J. C. Roach, C. M. Rosenberger, A. G. Rust, N. Yudkovsky, A. Aderem, I. Shmulevich, Uncovering a macrophage transcriptional program by integrating evidence from motif scanning and expression dynamics. PLoS Comput. Biol. 4, e1000021 (2008).
11. G. Oganesyan, S. K. Saha, B. Guo, J. Q. He, A. Shahangian, B. Zarnegar, A. Perry, G. Cheng, Critical role of TRAF3 in the Toll-like receptor-dependent and -independent antiviral response. Nature 439, 208-211 (2006).
12. I. Amit, M. Garber, N. Chevrier, A. P. Leite, Y. Donner, T. Eisenhaure, M. Guttman, J. K. Grenier, W. Li, O. Zuk, L. A. Schubert, B. Birditt, T. Shay, A. Goren, X. Zhang, Z. Smith, R. Deering, R. C. McDonald, M. Cabili, B. E. Bernstein, J. L. Rinn, A. Meissner, D. E. Root, N. Hacohen, A. Regev, Unbiased reconstruction of a mammalian transcriptional network mediating pathogen responses. Science 326, 257-263 (2009).
13. S. Akira, K. Takeda, Toll-like receptor signalling. Nat. Rev. Immunol. 4, 499-511 (2004).
14. S. Akira, S. Uematsu, O. Takeuchi, Pathogen recognition and innate immunity. Cell 124, 783-801 (2006).
15. R. Medzhitov, Origin and physiological roles of inflammation. Nature 454, 428-435 (2008).
16. T. Kawai, S. Akira, The role of pattern-recognition receptors in innate immunity: Update on Toll-like receptors. Nat. Immunol. 11, 373-384 (2010).
17. S. Sharma, B. R. tenOever, N. Grandvaux, G. P. Zhou, R. Lin, J. Hiscott, Triggering the interferon antiviral response through an IKK-related pathway. Science 300, 1148-1151 (2003).
18. Y. Fujii, T. Shimizu, M. Kusumoto, Y. Kyogoku, T. Taniguchi, T. Hakoshima, Crystal structure of an IRF-DNA complex reveals novel DNA recognition and cooperative binding to a tandem repeat of core sequences. EMBO J. 18, 5028-5041 (1999).
19. A. Hoffmann, G. Natoli, G. Ghosh, Transcriptional regulation via the NF-κB signaling module. Oncogene 25, 6706-6716 (2006).
20. S. Sanjabi, A. Hoffmann, H. C. Liou, D. Baltimore, S. T. Smale, Selective requirement for c-Rel during IL-12 P40 gene induction in macrophages. Proc. Natl. Acad. Sci. U.S.A. 97, 12705-12710 (2000).
21. A. Hoffmann, T. H. Leung, D. Baltimore, Genetic analysis of NF-κB/Rel transcription factors defines functional specificities. EMBO J. 22, 5530-5539 (2003).
22. + T lymphocytes. Science 256, 1452-1456 (1992).
23. R. M. Ten, C. V. Paya, N. Israel, O. Le Bail, M. G. Mattei, J. L. Virelizier, P. Kourilsky, A. Israel, The characterization of the promoter of the gene encoding the p50 subunit of NF-κB indicates that it participates in its own regulation. EMBO J. 11, 195-203 (1992).
24. D. Plaksin, P. A. Baeuerle, L. Eisenbach, KBF1 (p50 NF-κB homodimer) acts as a repressor of H-2Kb gene expression in metastatic tumor cells. J. Exp. Med. 177, 1651-1662 (1993).
25. H. C. Ledebur, T. P. Parks, Transcriptional regulation of the intercellular adhesion molecule-1 gene by inflammatory cytokines in human endothelial cells. Essential roles of a variant NF-κB site and p65 homodimers. J. Biol. Chem. 270, 933-943 (1995).
26. W. C. Sha, H. C. Liou, E. I. Tuomanen, D. Baltimore, Targeted disruption of the p50 subunit of NF-κB leads to multifocal defects in immune responses. Cell 80, 321-330 (1995).
27. I. A. Udalova, A. Richardson, A. Denys, C. Smith, H. Ackerman, B. Foxwell, D. Kwiatkowski, Functional consequences of a polymorphism affecting NF-κB p50-p50 binding to the TNF promoter region. Mol. Cell. Biol. 20, 9113-9119 (2000).
28. J. Bohuslav, V. V. Kravchenko, G. C. Parry, J. H. Erlich, S. Gerondakis, N. Mackman, R. J. Ulevitch, Regulation of an essential innate immune response by the p50 subunit of NF-κB. J. Clin. Invest. 102, 1645-1652 (1998).
29. H. C. Liou, G. P. Nolan, S. Ghosh, T. Fujita, D. Baltimore, The NF-κB p50 precursor, p105, contains an internal IkB-like inhibitor that preferentially inhibits p50. EMBO J. 11, 3003-3009 (1992).
30. M. R. Waterfield, M. Zhang, L. P. Norman, S. C. Sun, NF-κB1/p105 regulates lipopolysaccharide- stimulated MAP kinase signaling by governing the stability and function of the Tpl2 kinase. Mol. Cell 11, 685-694 (2003).
31. S. Beinke, J. Deka, V. Lang, M. P. Belich, P. A. Walker, S. Howell, S. J. Smerdon, S. J. Gamblin, S. C. Ley, NF-κB1 p105 negatively regulates TPL-2 MEK kinase activity. Mol. Cell. Biol. 23, 4739-4752 (2003).
32. M. Chang, A. J. Lee, L. Fitzpatrick, M. Zhang, S. C. Sun, NF-kB1 p105 regulates T cell homeostasis and prevents chronic inflammation. J. Immunol. 182, 3131-3138 (2009).
33. S. A. Koenig Merediz, M. Schmidt, G. J. Hoppe, J. Alfken, D. Meraro, B. Z. Levi, A. Neubauer, B. Wittig, Cloning of an interferon regulatory factor 2 isoform with different regulatory ability. Nucleic Acids Res. 28, 4219-4224 (2000).
34. P. C. Cogswell, R. I. Scheinman, A. S. Baldwin Jr., Promoter of the human NF-κB p50/p105 gene. Regulation by NF-κB subunits and by c-REL. J. Immunol. 150, 2794-2804 (1993).
35. Y. Q. Chen, S. Ghosh, G. Ghosh, A novel DNA recognition mode by the NF-κB p65 homodimer. Nat. Struct. Biol. 5, 67-73 (1998).
36. G. Ghosh, G. van Duyne, S. Ghosh, P. B. Sigler, Structure of NF-κB p50 homodimer bound to a κB site. Nature 373, 303-310 (1995).
37. L. Bintu, N. E. Buchler, H. G. Garcia, U. Gerland, T. Hwa, J. Kondev, R. Phillips, Transcriptional regulation by the numbers: Models. Curr. Opin. Genet. Dev. 15, 116-124 (2005).
38. A. S. Neish, M. A. Read, D. Thanos, R. Pine, T. Maniatis, T. Collins, Endothelial interferon regulatory factor 1 cooperates with NF-κB as a transcriptional activator of vascular cell adhesion molecule 1. Mol. Cell. Biol. 15, 2558-2569 (1995).
39. C. M. Fan, T. Maniatis, Two different virus-inducible elements are required for human b-interferon gene regulation. EMBO J. 8, 101-110 (1989).
40. M. Ptashne, A. Gann, Genes & Signals (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, 2002).
41. L. Bintu, N. E. Buchler, H. G. Garcia, U. Gerland, T. Hwa, J. Kondev, T. Kuhlman, R. Phillips, Transcriptional regulation by the numbers: Applications. Curr. Opin. Genet. Dev. 15, 125-135 (2005).
42. C. R. Escalante, E. Nistal-Villan, L. Shen, A. Garcia-Sastre, A. K. Aggarwal, Structure of IRF-3 bound to the PRDIII-I regulatory element of the human interferon-β enhancer. Mol. Cell 26, 703-716 (2007).
43. D. Thanos, T. Maniatis, Virus induction of human IFN β gene expression requires the assembly of an enhanceosome. Cell 83, 1091-1100 (1995).
44. B. S. Parekh, T. Maniatis, Virus infection leads to localized hyperacetylation of histones H3 and H4 at the IFN-b promoter. Mol. Cell 3, 125-129 (1999).
45. D. Panne, T. Maniatis, S. C. Harrison, An atomic model of the interferon-β enhanceosome. Cell 129, 1111-1123 (2007).
46. S. Mathys, T. Schroeder, J. Ellwart, U. H. Koszinowski, M. Messerle, U. Just, Dendritic cells under influence of mouse cytomegalovirus have a physiologic dual role: To initiate and to restrict T cell activation. J. Infect. Dis. 187, 988-999 (2003).
47. L. Wei, M. R. Sandbulte, P. G. Thomas, R. J. Webby, R. Homayouni, L. M. Pfeffer, NFκB negatively regulates interferon-induced gene expression and anti-influenza activity. J. Biol. Chem. 281, 11678-11684 (2006).
48. C. Kunsch, S. M. Ruben, C. A. Rosen, Selection of optimal κB/Rel DNA-binding motifs: Interaction of both subunits of NF-κB with DNA is required for transcriptional activation. Mol. Cell. Biol. 12, 4412-4421 (1992).
49. J. Schreiber, R. G. Jenner, H. L. Murray, G. K. Gerber, D. K. Gifford, R. A. Young, Coordinated binding of NF-κB family members in the response of human cells to lipopolysaccharide. Proc. Natl. Acad. Sci. U.S.A. 103, 5899-5904 (2006).
50. R. Martone, G. Euskirchen, P. Bertone, S. Hartman, T. E. Royce, N. M. Luscombe, J. L. Rinn, F. K. Nelson, P. Miller, M. Gerstein, S. Weissman, M. Snyder, Distribution of NF-κB-binding sites across human chromosome 22. Proc. Natl. Acad. Sci. U.S.A. 100, 12247-12252 (2003).
51. J. Ragoussis, S. Field, I. A. Udalova, Quantitative profiling of protein-DNA binding on microarrays. Methods Mol. Biol. 338, 261-280 (2006).
52. C. L. Warren, N. C. Kratochvil, K. E. Hauschild, S. Foister, M. L. Brezinski, P. B. Dervan, G. N. Phillips Jr., A. Z. Ansari, Defining the sequence-recognition profile of DNA-binding molecules. Proc. Natl. Acad. Sci. U.S.A. 103, 867-872 (2006).
53. S. J. Maerkl, S. R. Quake, A systems approach to measuring the binding energy landscapes of transcription factors. Science 315, 233-237 (2007).
54. G. Badis, M. F. Berger, A. A. Philippakis, S. Talukder, A. R. Gehrke, S. A. Jaeger, E. T. Chan, G. Metzler, A. Vedenko, X. Chen, H. Kuznetsov, C. F. Wang, D. Coburn, D. E. Newburger, Q. Morris, T. R. Hughes, M. L. Bulyk, Diversity and complexity in DNA recognition by transcription factors. Science 324, 1720-1723 (2009).
55. F. E. Chen, D. B. Huang, Y. Q. Chen, G. Ghosh, Crystal structure of p50/p65 heterodimer of transcription factor NF-κB bound to DNA. Nature 391, 410-413 (1998).
56. M. Carey, Y. S. Lin, M. R. Green, M. Ptashne, A mechanism for synergistic activation of a mammalian gene by GAL4 derivatives. Nature 345, 361-364 (1990).
57. A. H. Brivanlou, J. E. Darnell Jr., Signal transduction and the control of gene expression. Science 295, 813-818 (2002).
58. A. E. Mayo, Y. Setty, S. Shavit, A. Zaslaver, U. Alon, Plasticity of the cis-regulatory input function of a gene. PLoS Biol. 4, e45 (2006).
59. N. E. Buchler, U. Gerland, T. Hwa, On schemes of combinatorial transcription logic. Proc. Natl. Acad. Sci. U.S.A. 100, 5136-5141 (2003).
60. F. H. Lam, D. J. Steger, E. K. O'Shea, Chromatin decouples promoter threshold from dynamic range. Nature 453, 246-250 (2008).
61. S. Heinz, C. Benner, N. Spann, E. Bertolino, Y. C. Lin, P. Laslo, J. X. Cheng, C. Murre, H. Singh, C. K. Glass, Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol. Cell 38, 576-589 (2010).
62. A. Hsiao, T. Ideker, J. M. Olefsky, S. Subramaniam, VAMPIRE microarray suite: A web-based platform for the interpretation of gene expression data. Nucleic Acids Res. 33, W627-W632 (2005).
63. K. Cartharius, K. Frech, K. Grote, B. Klocke, M. Haltmeier, A. Klingenhoff, M. Frisch, M. Bayerlein, T. Werner, MatInspector and beyond: Promoter analysis based on transcription factor binding sites. Bioinformatics 21, 2933-2942 (2005).
64. S. L. Werner, D. Barken, A. Hoffmann, Stimulus specificity of gene expression programs determined by temporal control of IKK activity. Science 309, 1857-1861 (2005).
65. S. Basak, H. Kim, J. D. Kearns, V. Tergaonkar, E. O'Dea, S. L. Werner, C. A. Benedict, C. F. Ware, G. Ghosh, I. M. Verma, A. Hoffmann, A fourth IkB protein within the NF-kB signaling module. Cell 128, 369-381 (2007).
66. S. Ogawa, J. Lozach, K. Jepsen, D. Sawka-Verhelle, V. Perissi, R. Sasik, D. W. Rose, R. S. Johnson, M. G. Rosenfeld, C. K. Glass, A nuclear receptor corepressor transcriptional checkpoint controlling activator protein 1-dependent gene networks required for macrophage activation. Proc. Natl. Acad. Sci. U.S.A. 101, 14461-14466 (2004).
67. V. Perissi, A. Aggarwal, C. K. Glass, D. W. Rose, M. G. Rosenfeld, A corepressor/ coactivator exchange complex required for transcriptional activation by nuclear receptors and other regulated transcription factors. Cell 116, 511-526 (2004).
68. R. A. Garrick, T. G. Polefka, W. O. Cua, F. P. Chinard, Water permeability of alveolar macrophages. Am. J. Physiol. 251, C524-C528 (1986).
69. J. A. Swanson, M. Lee, P. E. Knapp, Cellular dimensions affecting the nucleocytoplasmic volume ratio. J. Cell Biol. 115, 941-948 (1991).
70. Acknowledgments: We thank G. Hardiman and the Biogem core facility and C. Glass for gene expression profiling; C. Benner for his motif search program (Homer); E. Chiang for TLR4-expressing HEK 293T cells; M. Asagiri and T. Huxford (San Diego State University) for the critical review of the manuscript; T. Hwa, V. Nizet, and C. Chang (University of Pennsylvania), as well as members of the laboratory, V. Wang, and V. Veckman for helpful discussions and support. Funding: Supported by the Graduate Program in Bioinformatics and Systems Biology and a Department of Defense Breast Cancer Predoctoral Training Fellowship (C.S.C.); the Biomedical Sciences Graduate Program (K.F.); and U.S. NIH grants to A.H. (P50-GM085764 and GM071573), G.G. and A.H. (GM085490), J.P. and A.H. (GM085325), C.A.B. (AI076864 and AI069298), and S.-C.S. (AI057555). Author contributions: C.S.C., J.L., K.F., and K.H. performed the experiments; C.S.C. performed computational work; M.C., S.-C.S., S.V., and C.A.B. provided critical reagents and protocols; C.S.C., K.F., and A.H. designed the experiments; C.S.C., K.F., A.H., D.-B.H., J.P., and G.G. analyzed the results; and C.S.C. and A.H. wrote the paper. Competing interests: The authors declare that they have no competing interests. Accession numbers: The gene expression array data have been deposited in the Gene Expression Omnibus database with the accession number GSE27112.