Transcription factors operate across disease loci, with EBNA2 implicated in autoimmunity

Nature Genetics

Volumn 50, Issue 5, 2018, Pages 699-707

  Harley, John B ^a,b,c   Chen, Xiaoting ^a   Pujato, Mario ^a   Miller, Daniel ^a   Maddox, Avery ^a   Forney, Carmy ^a   Magnusen, Albert F ^a   Lynch, Arthur ^a   Chetal, Kashish ^a   Yukawa, Masashi ^a   Barski, Artem ^a,b   Salomonis, Nathan ^a,b   Kaufman, Kenneth M ^a,b,c   Kottyan, Leah C ^a,b   Weirauch, Matthew T ^a,b  

^a CINCINNATI CHILDREN'S HOSPITAL MEDICAL CENTER   (United States)

^b UNIVERSITY OF CINCINNATI COLLEGE OF MEDICINE   (United States)

^c VETERANS AFFAIRS MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANDROGEN RECEPTOR; EPSTEIN BARR VIRUS ANTIGEN 2; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR GATA 3; DNA BINDING PROTEIN; EBNA-2 PROTEIN, HUMAN HERPESVIRUS 4; EPSTEIN BARR VIRUS ANTIGEN; PROTEIN BINDING; VIRAL PROTEIN;

ARTICLE; AUTOIMMUNITY; BREAST CANCER; CELIAC DISEASE; CHROMATIN IMMUNOPRECIPITATION; GENE EXPRESSION; GENE FREQUENCY; GENE LINKAGE DISEQUILIBRIUM; GENE LOCUS; GENETIC ASSOCIATION; GENETIC DISORDER; GENETIC VARIABILITY; GENOTYPE ENVIRONMENT INTERACTION; INFLAMMATORY BOWEL DISEASE; INSULIN DEPENDENT DIABETES MELLITUS; JUVENILE RHEUMATOID ARTHRITIS; MULTIPLE SCLEROSIS; PHENOTYPE; PRIORITY JOURNAL; PROSTATE CANCER; PROTEIN DNA BINDING; RHEUMATOID ARTHRITIS; SYSTEMIC LUPUS ERYTHEMATOSUS; CELL LINE; EPSTEIN BARR VIRUS; GENETICS; HUMAN; IMMUNOLOGY; MAXIMUM TOLERATED DOSE; NEOPLASM; REGULATORY SEQUENCE; TUMOR CELL LINE;

AUTOIMMUNITY; CELL LINE; CELL LINE, TUMOR; DNA-BINDING PROTEINS; EPSTEIN-BARR VIRUS NUCLEAR ANTIGENS; HERPESVIRUS 4, HUMAN; HUMANS; LUPUS ERYTHEMATOSUS, SYSTEMIC; MAXIMUM TOLERATED DOSE; NEOPLASMS; PHENOTYPE; PROTEIN BINDING; REGULATORY SEQUENCES, NUCLEIC ACID; TRANSCRIPTION FACTORS; VIRAL PROTEINS;

EID: 85045436990     PISSN: 10614036     EISSN: 15461718     Source Type: Journal    
DOI: 10.1038/s41588-018-0102-3     Document Type: Article

References (83)

1. Fujinami, R. S., von Herrath, M. G., Christen, U. & Whitton, J. L. Molecular mimicry, bystander activation, or viral persistence: infections and autoimmune disease. Clin. Microbiol. Rev. 19, 80-94 (2006).
2. Ercolini, A. M. & Miller, S. D. The role of infections in autoimmune disease. Clin. Exp. Immunol. 155, 1-15 (2009).
3. Sener, A. G. & Afsar, I. Infection and autoimmune disease. Rheumatol. Int. 32, 3331-3338 (2012).
4. James, J. A. et al. An increased prevalence of Epstein-Barr virus infection in young patients suggests a possible etiology for systemic lupus erythematosus. J. Clin. Invest. 100, 3019-3026 (1997).
5. Hanlon, P., Avenell, A., Aucott, L. & Vickers, M. A. Systematic review and meta-analysis of the sero-epidemiological association between Epstein-Barr virus and systemic lupus erythematosus. Arthritis Res. Ther. 16, R3 (2014).
6. McClain, M. T. et al. Early events in lupus humoral autoimmunity suggest initiation through molecular mimicry. Nat. Med. 11, 85-89 (2005).
7. Harley, J. B. & James, J. A. Epstein-Barr virus infection induces lupus autoimmunity. Bull. NYU Hosp. Jt. Dis. 64, 45-50 (2006).
8. Ascherio, A. & Munger, K. L. EBV and autoimmunity. Curr. Top. Microbiol. Immunol. 390, 365-385 (2015).
9. Draborg, A. H., Duus, K. & Houen, G. Epstein-Barr virus in systemic autoimmune diseases. Clin. Dev. Immunol. 2013, 535738 (2013).
10. Vaughn, S. E., Kottyan, L. C., Munroe, M. E. & Harley, J. B. Genetic susceptibility to lupus: the biological basis of genetic risk found in B cell signaling pathways. J. Leukoc. Biol. 92, 577-591 (2012).
11. Alarcón-Riquelme, M. E. et al. Genome-wide association study in an Amerindian ancestry population reveals novel systemic lupus erythematosus risk loci and the role of European admixture. Arthritis Rheumatol. 68, 932-943 (2016).
12. Bentham, J. et al. Genetic association analyses implicate aberrant regulation of innate and adaptive immunity genes in the pathogenesis of systemic lupus erythematosus. Nat. Genet. 47, 1457-1464 (2015).
13. Sun, C. et al. High-density genotyping of immune-related loci identifies new SLE risk variants in individuals with Asian ancestry. Nat. Genet. 48, 323-330 (2016).
14. Maurano, M. T. et al. Systematic localization of common disease-associated variation in regulatory DNA. Science 337, 1190-1195 (2012).
15. Hindorff, L. A. et al. Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proc. Natl. Acad. Sci. USA 106, 9362-9367 (2009).
16. Fang, H., Knezevic, B., Burnham, K. L. & Knight, J. C. XGR software for enhanced interpretation of genomic summary data, illustrated by application to immunological traits. Genome Med. 8, 129 (2016).
17. Schweizer, M. T. & Yu, E. Y. Persistent androgen receptor addiction in castration-resistant prostate cancer. J. Hematol. Oncol. 8, 128 (2015).
18. Asch-Kendrick, R. & Cimino-Mathews, A. The role of GATA3 in breast carcinomas: a review. Hum. Pathol. 48, 37-47 (2016).
19. Almohmeed, Y. H., Avenell, A., Aucott, L. & Vickers, M. A. Systematic review and meta-analysis of the sero-epidemiological association between Epstein Barr virus and multiple sclerosis. PLoS One 8, e61110 (2013).
20. Pender, M. P. & Burrows, S. R. Epstein-Barr virus and multiple sclerosis: potential opportunities for immunotherapy. Clin. Transl. Immunology 3, e27 (2014).
21. Márquez, A. C. & Horwitz, M. S. The role of latently infected B cells in CNS autoimmunity. Front. Immunol. 6, 544 (2015).
22. Ricigliano, V. A. et al. EBNA2 binds to genomic intervals associated with multiple sclerosis and overlaps with vitamin D receptor occupancy. PLoS One 10, e0119605 (2015).
23. Hu, X. et al. Integrating autoimmune risk loci with gene-expression data identifies specific pathogenic immune cell subsets. Am. J. Hum. Genet. 89, 496-506 (2011).
24. Trynka, G. et al. Disentangling the effects of colocalizing genomic annotations to functionally prioritize non-coding variants within complextrait loci. Am. J. Hum. Genet. 97, 139-152 (2015).
25. Zhou, H. et al. Epstein-Barr virus oncoprotein super-enhancers control B cell growth. Cell Host Microbe 17, 205-216 (2015).
26. Gewurz, B. E. et al. Canonical NF-? B activation is essential for Epstein-Barr virus latent membrane protein 1 TES2/CTAR2 gene regulation. J. Virol. 85, 6764-6773 (2011).
27. Ersing, I., Bernhardt, K. & Gewurz, B. E. NF-? B and IRF7 pathway activation by Epstein-Barr virus Latent Membrane Protein 1. Viruses 5, 1587-1606 (2013).
28. Price, A. M. et al. Analysis of Epstein-Barr virus-regulated host gene expression changes through primary B-cell outgrowth reveals delayed kinetics of latent membrane protein 1-mediated NF-? B activation. J. Virol. 86, 11096-11106 (2012).
29. Welter, D. et al. The NHGRI GWAS Catalog, a curated resource of SNP-trait associations. Nucleic Acids Res. 42, D1001-D1006 (2014).
30. Farh, K. K. et al. Genetic and epigenetic fine mapping of causal autoimmune disease variants. Nature 518, 337-343 (2015).
31. Zimber-Strobl, U. et al. Epstein-Barr virus nuclear antigen 2 exerts its transactivating function through interaction with recombination signal binding protein RBP-J? , the homologue of Drosophila Suppressor of Hairless. EMBO J. 13, 4973-4982 (1994).
32. Grossman, S. R., Johannsen, E., Tong, X., Yalamanchili, R. & Kieff, E. The Epstein-Barr virus nuclear antigen 2 transactivator is directed to response elements by the J kappa recombination signal binding protein. Proc. Natl. Acad. Sci. USA 91, 7568-7572 (1994).
33. Henkel, T., Ling, P. D., Hayward, S. D. & Peterson, M. G. Mediation of Epstein-Barr virus EBNA2 transactivation by recombination signal-binding protein J kappa. Science 265, 92-95 (1994).
34. Scala, G. et al. Epstein-Barr virus nuclear antigen 2 transactivates the long terminal repeat of human immunodeficiency virus type 1. J. Virol. 67, 2853-2861 (1993).
35. Wang, J. H. et al. Aiolos regulates B cell activation and maturation to effector state. Immunity 9, 543-553 (1998).
36. Lu, F. et al. EBNA2 drives formation of new chromosome binding sites and target genes for B-cell master regulatory transcription factors RBP-j? and EBF1. PLoS Pathog. 12, e1005339 (2016).
37. Bailey, S. D., Virtanen, C., Haibe-Kains, B. & Lupien, M. ABC: a tool to identify SNVs causing allele-specific transcription factor binding from ChIP-Seq experiments. Bioinformatics 31, 3057-3059 (2015).
38. Buchkovich, M. L. et al. Removing reference mapping biases using limited or no genotype data identifies allelic differences in protein binding at disease-associated loci. BMC Med. Genomics 8, 43 (2015).
39. Kumasaka, N., Knights, A. J. & Gaffney, D. J. Fine-mapping cellular QTLs with RASQUAL and ATAC-seq. Nat. Genet. 48, 206-213 (2016).
40. Shi, W., Fornes, O., Mathelier, A. & Wasserman, W. W. Evaluating the impact of single nucleotide variants on transcription factor binding. Nucleic Acids Res. 44, 10106-10116 (2016).
41. Ma, B., Huang, J. & Liang, L. RTeQTL: real-time online engine for expression quantitative trait loci analyses. Database (Oxford) 2014, bau066 https://doi. org/10.1093/database/bau066 (2014).
42. Kryworuckho, M., Diaz-Mitoma, F. & Kumar, A. CD44 isoforms containing exons V6 and V7 are differentially expressed on mitogenically stimulated normal and Epstein-Barr virus-transformed human B cells. Immunology 86, 41-48 (1995).
43. Gonnella, R. et al. PKC theta and p38 MAPK activate the EBV lytic cycle through autophagy induction. Biochim. Biophys. Acta 1853, 1586-1595 (2015).
44. Ernst, J. et al. Mapping and analysis of chromatin state dynamics in nine human cell types. Nature 473, 43-49 (2011).
45. Griffith, M. et al. DGIdb: mining the druggable genome. Nat. Methods 10, 1209-1210 (2013).
46. Harter, M. R. et al. BS69/ZMYND11 C-terminal domains bind and inhibit EBNA2. PLoS Pathog. 12, e1005414 (2016).
47. Li, Y. et al. A genome-wide association study in Han Chinese identifies a susceptibility locus for primary Sjögren's syndrome at 7q11.23. Nat. Genet. 45, 1361-1365 (2013).
48. Okada, Y. et al. Genetics of rheumatoid arthritis contributes to biology and drug discovery. Nature 506, 376-381 (2014).
49. GTEx Consortium. The Genotype-Tissue Expression (GTEx) pilot analysis: multitissue gene regulation in humans. Science 348, 648-660 (2015).
50. Mifsud, B. et al. Mapping long-range promoter contacts in human cells with high-resolution capture Hi-C. Nat. Genet. 47, 598-606 (2015).
51. Javierre, B. M. et al. Lineage-specific genome architecture links enhancers and non-coding disease variants to target gene promoters. Cell 167, 1369-1384.e19 (2016).
52. Liang, L. et al. A cross-platform analysis of 14,177 expression quantitative trait loci derived from lymphoblastoid cell lines. Genome Res. 23, 716-726 (2013).
53. Stranger, B. E. et al. Population genomics of human gene expression. Nat. Genet. 39, 1217-1224 (2007).
54. Veyrieras, J. B. et al. High-resolution mapping of expression-QTLs yields insight into human gene regulation. PLoS Genet. 4, e1000214 (2008).
55. Pickrell, J. K. et al. Understanding mechanisms underlying human gene expression variation with RNA sequencing. Nature 464, 768-772 (2010).
56. Montgomery, S. B. et al. Transcriptome genetics using second generation sequencing in a Caucasian population. Nature 464, 773-777 (2010).
57. Mangravite, L. M. et al. A statin-dependent QTL for GATM expression is associated with statin-induced myopathy. Nature 502, 377-380 (2013).
58. Dimas, A. S. et al. Common regulatory variation impacts gene expression in a cell type-dependent manner. Science 325, 1246-1250 (2009).
59. Gaffney, D. J. et al. Dissecting the regulatory architecture of gene expression QTLs. Genome Biol. 13, R7 (2012).
60. Trynka, G. et al. Dense genotyping identifies and localizes multiple common and rare variant association signals in celiac disease. Nat. Genet. 43, 1193-1201 (2011).
61. Purcell, S. et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am. J. Hum. Genet. 81, 559-575 (2007).
62. ENCODE Project Consortium. An integrated encyclopedia of DNA elements in the human genome. Nature 489, 57-74 (2012).
63. Kundaje, A. et al. Integrative analysis of 111 reference human epigenomes. Nature 518, 317-330 (2015).
64. Liu, T. et al. Cistrome: an integrative platform for transcriptional regulation studies. Genome Biol. 12, R83 (2011).
65. Portales-Casamar, E. et al. The PAZAR database of gene regulatory information coupled to the ORCA toolkit for the study of regulatory sequences. Nucleic Acids Res. 37, D54-D60 (2009).
66. Griffon, A. et al. Integrative analysis of public ChIP-seq experiments reveals a complex multi-cell regulatory landscape. Nucleic Acids Res. 43, e27 (2015).
67. Barrett, T. et al. NCBI GEO: archive for functional genomics data sets-update. Nucleic Acids Res. 41, D991-D995 (2013).
68. Weirauch, M. T. et al. Determination and inference of eukaryotic transcription factor sequence specificity. Cell 158, 1431-1443 (2014).
69. 1000 Genomes Project Consortium et al. A global reference for human genetic variation. Nature 526, 68-74 (2015).
70. Smigielski, E. M., Sirotkin, K., Ward, M. & Sherry, S. T. dbSNP: a database of single nucleotide polymorphisms. Nucleic Acids Res. 28, 352-355 (2000).
71. Kottyan, L. C. et al. Genome-wide association analysis of eosinophilic esophagitis provides insight into the tissue specificity of this allergic disease. Nat. Genet. 46, 895-900 (2014).
72. Verma, S. S. et al. Imputation and quality control steps for combining multiple genome-wide datasets. Front. Genet. 5, 370 (2014).
73. Langmead, B. & Salzberg, S. L. Fast gapped-read alignment with Bowtie 2. Nat. Methods 9, 357-359 (2012).
74. Trapnell, C., Pachter, L. & Salzberg, S. L. TopHat: discovering splice junctions with RNA-Seq. Bioinformatics 25, 1105-1111 (2009).
75. Flicek, P. et al. Ensembl 2013. Nucleic Acids Res. 41, D48-D55 (2013).
76. Kim, D., Langmead, B. & Salzberg, S. L. HISAT: a fast spliced aligner with low memory requirements. Nat. Methods 12, 357-360 (2015).
77. Trapnell, C. et al. Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nat. Biotechnol. 28, 511-515 (2010).
78. Birkenbach, M., Josefsen, K., Yalamanchili, R., Lenoir, G. & Kieff, E. Epstein-Barr virus-induced genes: first lymphocyte-specific G protein-coupled peptide receptors. J. Virol. 67, 2209-2220 (1993).
79. Chen, C. C. et al. NF-? B-mediated transcriptional upregulation of TNFAIP2 by the Epstein-Barr virus oncoprotein, LMP1, promotes cell motility in nasopharyngeal carcinoma. Oncogene 33, 3648-3659 (2014).
80. Craig, F. E. et al. Gene expression profiling of Epstein-Barr virus-positive and-negative monomorphic B-cell posttransplant lymphoproliferative disorders. Diagn. Mol. Pathol. 16, 158-168 (2007).
81. Smith, N. et al. Induction of interferon-stimulated genes on the IL-4 response axis by Epstein-Barr virus infected human B cells; relevance to cellular transformation. PLoS One 8, e64868 (2013). 8.
82. Portis, T., Dyck, P. & Longnecker, R. Epstein-Barr virus (EBV) LMP2A induces alterations in gene transcription similar to those observed in Reed-Sternberg cells of Hodgkin lymphoma. Blood 102, 4166-4178 (2003).
83. Lee, I. S., Shin, Y. K., Chung, D. H. & Park, S. H. LMP1-induced downregulation of CD99 molecules in Hodgkin and Reed-Sternberg cells. Leuk. Lymphoma 42, 587-594 (2001).