The genetic association of RUNX3 with ankylosing spondylitis can be explained by allele-specific effects on IRF4 recruitment that alter gene expression

Annals of the Rheumatic Diseases

Volumn 75, Issue 8, 2016, Pages 1534-1540

  Vecellio, Matteo ^a,b   Roberts, Amity R ^a,b   Cohen, Carla J ^a,b   Cortes, Adrian ^a,c   Knight, Julian C ^c   Bowness, Paul ^a,b   Wordsworth, B Paul ^a,b  

^a UNIVERSITY OF OXFORD   (United Kingdom)

^b NIHR OXFORD BIOMEDICAL RESEARCH CENTRE   (United Kingdom)

^c UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

Ankylosing Spondylitis; Gene Polymorphism; Spondyloarthritis; T Cells

Indexed keywords

INTERFERON REGULATORY FACTOR 4; MESSENGER RNA; NONSTEROID ANTIINFLAMMATORY AGENT; SALAZOSULFAPYRIDINE; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR RUNX3; INTERFERON REGULATORY FACTOR; INTERFERON REGULATORY FACTOR-4; RUNX3 PROTEIN, HUMAN;

ADULT; AGED; ALLELE; ANKYLOSING SPONDYLITIS; ARTICLE; BINDING SITE; CD8+ T LYMPHOCYTE; CHROMATIN ASSEMBLY AND DISASSEMBLY; CHROMATIN IMMUNOPRECIPITATION; CLINICAL ARTICLE; CONTROLLED STUDY; FEMALE; GEL MOBILITY SHIFT ASSAY; GENE CONSTRUCT; GENE EXPRESSION; GENETIC ASSOCIATION; GENOTYPE; HISTONE METHYLATION; HUMAN; IMMUNOCOMPETENT CELL; JURKAT CELL LINE; LUCIFERASE ASSAY; MALE; PRIORITY JOURNAL; PROMOTER REGION; REAL TIME POLYMERASE CHAIN REACTION; REPORTER GENE; SINGLE NUCLEOTIDE POLYMORPHISM; BIOSYNTHESIS; CELL CULTURE; GENE EXPRESSION REGULATION; GENETIC PREDISPOSITION; GENETICS; GENOTYPING TECHNIQUE; IMMUNOLOGY; METABOLISM; MIDDLE AGED; PROCEDURES;

ADULT; AGED; CD8-POSITIVE T-LYMPHOCYTES; CELLS, CULTURED; CORE BINDING FACTOR ALPHA 3 SUBUNIT; ELECTROPHORETIC MOBILITY SHIFT ASSAY; GENE EXPRESSION REGULATION; GENES, REPORTER; GENETIC PREDISPOSITION TO DISEASE; GENOTYPING TECHNIQUES; HUMANS; INTERFERON REGULATORY FACTORS; MIDDLE AGED; POLYMORPHISM, SINGLE NUCLEOTIDE; REAL-TIME POLYMERASE CHAIN REACTION; RNA, MESSENGER; SPONDYLITIS, ANKYLOSING; TRANSCRIPTION FACTORS;

EID: 84982855932     PISSN: 00034967     EISSN: 14682060     Source Type: Journal    
DOI: 10.1136/annrheumdis-2015-207490     Document Type: Article

References (47)

1. Cortes A, Hadler J, Pointon JP, et al., International Genetics of Ankylosing Spondylitis Consortium (IGAS). Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related loci. Nat Genet 2013;45:730-8.
2. Evans DM, Spencer CC, Pointon JJ, et al. Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility. Nat Genet 2011;43:761-7.
3. Karaderi T, Harvey D, Farrar C, et al. Association between the interleukin 23 receptor and ankylosing spondylitis is confirmed by a new UK case-control study and meta-Analysis of published series. Rheumatology (Oxford) 2009;48:386-9.
4. Harvey D, Pointon JJ, Evans DM, et al. Investigating the genetic association between ERAP1 and ankylosing spondylitis. Hum Mol Genet 2009;18:4204-12.
5. Hindorff LA, Sethupathy P, Junkins HA, et al. Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proc Natl Acad Sci USA 2009;106:9362-7.
6. Apel M, Uebe S, Bowes J, et al. Variants in RUNX3 contribute to susceptibility to psoriatic arthritis, exhibiting further common ground with ankylosing spondylitis. Arthritis Rheum 2013;65:1224-31.
7. Schaub MA, Boyle AP, Kundaje A, et al. Linking disease associations with regulatory information in the human genome. Genome Res 2012;22:1748-59.
8. Cohen MM Jr. Perspectives on RUNX genes: An update. Am J Med Genet 2009; 149:2629-46.
9. Lotem J, Levanon D, Negreanu V, et al. Runx3 at the interface of immunity, inflammation and cancer. Biochim Biophys Acta 2015;1855:131-43.
10. Levanon D, Negreanu V, Lotem J, et al. Transcription factor Runx3 regulates interleukin-15-dependent natural killer cell activation. Mol Cell Biol 2014;34:1158-69.
11. Sugai M, Aoki K, Osato M, et al. Runx3 is required for full activation of regulatory T cells to prevent colitis-Associated tumor formation. J Immunol 2011;186: 6515-20.
12. Taniuchi I, Osato M, Egawa T, et al. Differential requirements for Runx proteins in CD4 repression and epigenetic silencing during T lymphocyte development. Cell 2002;111:621-33.
13. Cruz-Guilloty F, Pipkin ME, Djuretic IM, et al. Runx3 and T-box proteins cooperate to establish the transcriptional program of effector CTLs. J Exp Med 2009;206:51-9.
14. Rini D, Calabi F. Identification and comparative analysis of a second RUNX3 promoter. Gene 2001;273:13-22.
15. Bangsow C, Rubins N, Glusman G, et al. The RUNX3 gene sequence, structure and regulated expression. Gene 2001;279:221-32.
16. Han H, Cortez CC, Yang X, et al. DNA methylation directly silences genes with non-CpG island promoters and establishes a nucleosome occupied promoter. Hum Mol Genet 2011;20:4299-310.
17. Paluszczak J, Sarbak J, Kostrzewska-Poczekaj M, et al. The negative regulators of Wnt pathway-DACH1, DKK1, and WIF1 are methylated in oral and oropharyngeal cancer and WIF1 methylation predicts shorter survival. Tumour Biol 2015;36:2855-61.
18. Estécio MR, Maddipoti S, Bueso-Ramos C, et al. RUNX3 promoter hypermethylation is frequent in leukaemia cell lines and associated with acute myeloid leukaemia inv (16) subtype. Br J Haematol 2015;169:344-51.
19. Guo C, Ren F, Wang D, et al. RUNX3 is inactivated by promoter hypermethylation in malignant transformation of ovarian endometriosis. Oncol Rep 2014;32:2580-8.
20. ENCODE Project Consortium. A users guide to the encyclopedia of DNA elements (ENCODE). PLoS Biol 2011;9:e1001046.
21. Delaneau O, Zagury JF, Marchini J. Improved whole chromosome phasing for disease and population genetic studies. Nat Methods 2013;10:5-6.
22. Abecasis GR, Auton A, Brooks LD, et al., 1000 Genomes Project Consortium. An integrated map of genetic variation from 1,092 human genomes. Nature 2012;491:56-65.
23. Howie B, Fuchsberger C, Stephens M, et al. Fast and accurate genotype imputation in genome-wide association studies through pre-phasing. Nat Genet 2012;44:955-9.
24. Howie BN, Donnelly P, Marchini J. A flexible and accurate genotype imputation method for the next generation of genome-wide association studies. PLoS Genet 2009;5:e1000529.
25. Van der Linden S, Valkenburg HA, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum 1984;27:361-8.
26. Garrett S, Jenkinson T, Kennedy LG, et al. A new approach to defining disease status in ankylosing spondylitis: The Bath Ankylosing Spondylitis Disease Activity Index. J Rheumatol 1994;21:2286-91.
27. Purcell S, Neale B, Todd-Brown K, et al. PLINK: A tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 2007;81:559-75.
28. ENCODE Project Consortium. An integrated encyclopedia of DNA elements in the human genome. Nature 2012;489:57-74.
29. Lotem J, Levanon D, Negreanu V, et al. Runx3-mediated transcriptional program in cytotoxic lymphocytes. PLoS ONE 2013;8:e80467.
30. Yao S, Buzo BF, Pham D, et al. Interferon regulatory factor 4 sustains CD8(+) T cell expansion and effector differentiation. Immunity 2013;39:833-45.
31. Man K, Miasari M, Shi W, et al. The transcription factor IRF4 is essential for TCR affinity-mediated metabolic programming and clonal expansion of T cells. Nat Immunol 2013;14:1155-65.
32. Cao Y, Li H, Sun Y, et al. Interferon regulatory factor 4 regulates thymocyte differentiation by repressing Runx3 expression. Eur J Immunol 2010;40:3198-209.
33. Nayar R, Schutten E, Bautista B, et al. Graded levels of IRF4 regulate CD8+T cell differentiation and expansion, but not attrition, in response to acute virus infection. J Immunol 2014;192:5881-93.
34. Fainaru O, Woolf E, Lotem J, et al. Runx3 regulates mouse TGF-beta-mediated dendritic cell function and its absence results in airway inflammation. EMBO J 2004;23:969-79.
35. Collins PL, Chang S, Henderson M, et al. Distal regions of the human IFNG locus direct cell type-specific expression. J Immunol 2010;185:1492-501.
36. Fiorillo MT, Maragno M, Butler R, et al. CD8(+) T-cell autoreactivity to an HLA-B27-restricted self-epitope correlates with ankylosing spondylitis. J Clin Invest 2000;106:47-53.
37. Schirmer M, Goldberger C, Wörzner R, et al. Circulating cytotoxic CD8(+) CD28(-) T cells in ankylosing spondylitis. Arthritis Res 2002;4:71-6.
38. Taurog JD, Richardson JA, Croft JT, et al. The germfree state prevents development of gut and joint inflammatory disease in HLA-B27 transgenic rats. J Exp Med 1994;180:2359-64.
39. Taurog JD, Dorris ML, Satumtira N, et al. Spondylarthritis in HLA-B27/human beta2-microglobulin-Transgenic rats is not prevented by lack of CD8. Arthritis Rheum 2009;60:1977-84.
40. Chan AT, Kollnberger SD, Wedderburn LR, et al. Expansion and enhanced survival of natural killer cells expressing the killer immunoglobulin-like receptor KIR3DL2 in spondylarthritis. Arthritis Rheum 2005;52:3586-95.
41. Overgaard NH, Jung J, Steptoe RJ, et al. CD4+/CD8+ double-positive T cells: more than just a developmental stage? J Leukoc Biol 2015;97:31-8.
42. Boyle LH, Goodall JC, Gaston JS. The recognition of abnormal forms of HLA-B27 by CD4+ T cells. Curr Mol Med 2004;4:51-8.
43. Jansen DT, Hameetman M, van Bergen J, et al. IL-17-producing CD4+ T cells are increased in early, active axial spondyloarthritis including patients without imaging abnormalities. Rheumatology (Oxford) 2015;54:728-35.
44. Shen H, Goodall JC, Gaston JS. Frequency and phenotype of T helper 17 cells in peripheral blood and synovial fluid of patients with reactive arthritis. J Rheumatol 2010;37:2096-9.
45. Ghoussaini M, Edwards SL, Michailidou K, et al. Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation. Nat Commun 2014;4:4999.
46. Huang Q, Whitington T, Gao P, et al. A prostate cancer susceptibility allele at 6q22 increases RFX6 expression by modulating HOXB13 chromatin binding. Nat Genet 2014;46:126-35.
47. Ciofani M, Madar A, Galan C, et al. A validated regulatory network for Th17 cell specification. Cell 2012;151:289-303.