MYC activation and BCL2L11 silencing by a tumour virus through the large-scale reconfiguration of enhancer-promoter hubs

eLife

Volumn 5, Issue AUGUST, 2016, Pages

  Wood, C David ^a   Veenstra, Hildegonda ^a   Khasnis, Sarika ^a   Gunnell, Andrea ^a   Webb, Helen M ^a   Shannon Lowe, Claire ^b   Andrews, Simon ^c   Osborne, Cameron S ^d   West, Michelle J ^a  

^a UNIVERSITY OF SUSSEX   (United Kingdom)

^b UNIVERSITY OF BIRMINGHAM   (United Kingdom)

^c BABRAHAM INSTITUTE   (United Kingdom)

^d GUY S HOSPITAL   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

BRG1 PROTEIN; EPSTEIN BARR VIRUS ANTIGEN 2; EPSTEIN BARR VIRUS ANTIGEN 3; EPSTEIN BARR VIRUS ANTIGEN 3C; TRANSCRIPTION FACTOR EZH2; UNCLASSIFIED DRUG; VIRUS ANTIGEN; BIM PROTEIN; DNA HELICASE; EPSTEIN BARR VIRUS ANTIGEN; MYC PROTEIN; NUCLEAR PROTEIN; PROTEIN BINDING; REPRESSOR PROTEIN; SMARCA4 PROTEIN, HUMAN; TRANSACTIVATOR PROTEIN; TRANSCRIPTION FACTOR;

ACOXL GENE; APOPTOSIS; ARTICLE; B CELL LYMPHOMA; B CELL LYMPHOMA 2L11 GENE; CASPASE ASSAY; CELL SURVIVAL; CONTROLLED STUDY; ENZYME ACTIVITY; EPSTEIN BARR VIRUS; GENE; GENE ACTIVATION; GENE EXPRESSION; GENE LOCATION; GENE LOCUS; GENE SEQUENCE; GENE SILENCING; HUMAN; HUMAN CELL; IMMUNOBLOTTING; MOLECULAR INTERACTION; ONCOGENE MYC; PROTON TRANSPORT; REAL TIME POLYMERASE CHAIN REACTION; ENZYMOLOGY; GENETICS; METABOLISM; PHYSIOLOGY; PROMOTER REGION; TRANSCRIPTION INITIATION;

BCL-2-LIKE PROTEIN 11; DNA HELICASES; EPSTEIN-BARR VIRUS NUCLEAR ANTIGENS; GENE SILENCING; HERPESVIRUS 4, HUMAN; NUCLEAR PROTEINS; PROMOTER REGIONS, GENETIC; PROTEIN BINDING; PROTO-ONCOGENE PROTEINS C-MYC; REPRESSOR PROTEINS; TRANS-ACTIVATORS; TRANSCRIPTION FACTORS; TRANSCRIPTIONAL ACTIVATION;

EID: 84985914211     PISSN: None     EISSN: 2050084X     Source Type: Journal    
DOI: 10.7554/eLife.18270     Document Type: Article

References (79)

1. Ahmadiyeh N, Pomerantz MM, Grisanzio C, Herman P, Jia L, Almendro V, He HH, Brown M, Liu XS, Davis M, Caswell JL, Beckwith CA, Hills A, MacConaill L, Coetzee GA, Regan MM, Freedman ML. 2010. 8q24 prostate, breast, and colon cancer risk loci show tissue-specific long-range interaction with MYC. PNAS 107:9742–9746. doi:10.1073/pnas.0910668107.
2. Allday MJ, Bazot Q, White RE. 2015. The EBNA3 family: Two oncoproteins and a tumour suppressor that are central to the biology of EBV in B cells. Current Topics in Microbiology and Immunology 391:61–117. doi:10.1007/978-3-319-22834-1_3.
3. Ambs S, Prueitt RL, Yi M, Hudson RS, Howe TM, Petrocca F, Wallace TA, Liu CG, Volinia S, Calin GA, Yfantis HG, Stephens RM, Croce CM. 2008. Genomic profiling of microRNA and messenger RNA reveals deregulated microRNA expression in prostate cancer. Cancer Research 68:6162–6170. doi:10.1158/0008-5472.CAN-08-0144.
4. Anderton E, Yee J, Smith P, Crook T, White RE, Allday MJ. 2008. Two Epstein-Barr virus (EBV) oncoproteins cooperate to repress expression of the proapoptotic tumour-suppressor Bim: clues to the pathogenesis of Burkitt’s lymphoma. Oncogene 27:421–433. doi:10.1038/sj.onc.1210668.
5. Bark-Jones SJ, Webb HM, West MJ. 2006. EBV EBNA 2 stimulates CDK9-dependent transcription and RNA polymerase II phosphorylation on serine 5. Oncogene 25:1775–1785. doi:10.1038/sj.onc.1209205.
6. Berndt SI, Skibola CF, Joseph V, Camp NJ, Nieters A, Wang Z, Cozen W, Monnereau A, Wang SS, Kelly RS, Lan Q, Teras LR, Chatterjee N, Chung CC, Yeager M, Brooks-Wilson AR, Hartge P, Purdue MP, Birmann BM, Armstrong BK, et al. 2013. Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia. Nature Genetics 45:868–876. doi:10.1038/ng.2652.
7. Boerma EG, Siebert R, Kluin PM, Baudis M. 2009. Translocations involving 8q24 in Burkitt lymphoma and other malignant lymphomas: a historical review of cytogenetics in the light of todays knowledge. Leukemia 23:225–234. doi:10.1038/leu.2008.281.
8. Busch K, Keller T, Fuchs U, Yeh RF, Harbott J, Klose I, Wiemels J, Novosel A, Reiter A, Borkhardt A. 2007. Identification of two distinct MYC breakpoint clusters and their association with various IGH breakpoint regions in the t(8;14) translocations in sporadic Burkitt-lymphoma. Leukemia 21:1739–1751. doi:10.1038/sj.leu.2404753.
9. Cohen JI, Wang F, Mannick J, Kieff E. 1989. Epstein-Barr virus nuclear protein 2 is a key determinant of lymphocyte transformation. PNAS 86:9558–9562. doi:10.1073/pnas.86.23.9558.
10. Di Bernardo MC, Crowther-Swanepoel D, Broderick P, Webb E, Sellick G, Wild R, Sullivan K, Vijayakrishnan J, Wang Y, Pittman AM, Sunter NJ, Hall AG, Dyer MJ, Matutes E, Dearden C, Mainou-Fowler T, Jackson GH, Summerfield G, Harris RJ, Pettitt AR, et al. 2008. A genome-wide association study identifies six susceptibility loci for chronic lymphocytic leukemia. Nature Genetics 40:1204–1210. doi:10.1038/ng.219.
11. Dorsett Y, Robbiani DF, Jankovic M, Reina-San-Martin B, Eisenreich TR, Nussenzweig MC. 2007. A role for AID in chromosome translocations between c-myc and the IgH variable region. The Journal of Experimental Medicine 204:2225–2232. doi:10.1084/jem.20070884.
12. Egle A, Harris AW, Bouillet P, Cory S. 2004. Bim is a suppressor of Myc-induced mouse B cell leukemia. PNAS 101:6164–6169. doi:10.1073/pnas.0401471101.
13. Epstein MA, Achong BG, Barr YM. 1964. Virus particles in cultured lymphoblasts from burkitt’s lymphoma. The Lancet 283:702–703. doi:10.1016/s0140-6736(64)91524-7.
14. Gregory CD, Rowe M, Rickinson AB. 1990. Different Epstein-Barr virus-B cell interactions in phenotypically distinct clones of a Burkitt’s lymphoma cell line. Journal of General Virology 71:1481–1495. doi:10.1099/0022-1317-71-7-1481.
15. Gudmundsson J, Sulem P, Gudbjartsson DF, Blondal T, Gylfason A, Agnarsson BA, Benediktsdottir KR, Magnusdottir DN, Orlygsdottir G, Jakobsdottir M, Stacey SN, Sigurdsson A, Wahlfors T, Tammela T, Breyer JP, McReynolds KM, Bradley KM, Saez B, Godino J, Navarrete S, et al. 2009. Genome-wide association and replication studies identify four variants associated with prostate cancer susceptibility. Nature Genetics 41: 1122–1126. doi:10.1038/ng.448.
16. Gudmundsson J, Sulem P, Gudbjartsson DF, Masson G, Agnarsson BA, Benediktsdottir KR, Sigurdsson A, Magnusson OT, Gudjonsson SA, Magnusdottir DN, Johannsdottir H, Helgadottir HT, Stacey SN, Jonasdottir A, Olafsdottir SB, Thorleifsson G, Jonasson JG, Tryggvadottir L, Navarrete S, Fuertes F, et al. 2012. A study based on whole-genome sequencing yields a rare variant at 8q24 associated with prostate cancer. Nature Genetics 44:1326–1329. doi:10.1038/ng.2437.
17. Gunnell A, Webb HM, Wood CD, McClellan MJ, Wichaidit B, Kempkes B, Jenner RG, Osborne C, Farrell PJ, West MJ. 2016. RUNX super-enhancer control through the Notch pathway by Epstein-Barr virus transcription factors regulates B cell growth. Nucleic Acids Research 44:4636–4650. doi:10.1093/nar/gkw085.
18. Haluska FG, Finver S, Tsujimoto Y, Croce CM. 1986. The t(8; 14) chromosomal translocation occurring in B-cell malignancies results from mistakes in V-D-J joining. Nature 324:158–161. doi:10.1038/324158a0.
19. Harth-Hertle ML, Scholz BA, Erhard F, Glaser LV, Dölken L, Zimmer R, Kempkes B. 2013. Inactivation of intergenic enhancers by EBNA3A initiates and maintains polycomb signatures across a chromatin domain encoding CXCL10 and CXCL9. PLoS Pathogens 9:e1003638. doi:10.1371/journal.ppat.1003638.
20. Herranz D, Ambesi-Impiombato A, Palomero T, Schnell SA, Belver L, Wendorff AA, Xu L, Castillo-Martin M, Llobet-Navás D, Cordon-Cardo C, Clappier E, Soulier J, Ferrando AA. 2014. A NOTCH1-driven MYC enhancer promotes T cell development, transformation and acute lymphoblastic leukemia. Nature Medicine 20:1130–1137. doi:10.1038/nm.3665.
21. Hertle ML, Popp C, Petermann S, Maier S, Kremmer E, Lang R, Mages J, Kempkes B. 2009. Differential gene expression patterns of EBV infected EBNA-3A positive and negative human B lymphocytes. PLoS Pathogens 5: e1000506. doi:10.1371/journal.ppat.1000506.
22. Jiang S, Willox B, Zhou H, Holthaus AM, Wang A, Shi TT, Maruo S, Kharchenko PV, Johannsen EC, Kieff E, Zhao B. 2014. Epstein-Barr virus nuclear antigen 3C binds to BATF/IRF4 or SPI1/IRF4 composite sites and recruits Sin3A to repress CDKN2A. PNAS 111:421–426. doi:10.1073/pnas.1321704111.
23. Johannsen E, Koh E, Mosialos G, Tong X, Kieff E, Grossman SR. 1995. Epstein-Barr virus nuclear protein 2 transactivation of the latent membrane protein 1 promoter is mediated by J kappa and PU.1. Journal of Virology 69:253–262.
24. Joos S, Haluska FG, Falk MH, Henglein B, Hameister H, Croce CM, Bornkamm GW. 1992. Mapping chromosomal breakpoints of Burkitt’s t(8;14) translocations far upstream of c-myc. Cancer Research 52:6547–6552.
25. Kaiser C, Laux G, Eick D, Jochner N, Bornkamm GW, Kempkes B. 1999. The proto-oncogene c-myc is a direct target gene of Epstein-Barr virus nuclear antigen 2. Journal of Virology 73:4481–4484.
26. Kalchschmidt JS, Bashford-Rogers R, Paschos K, Gillman AC, Styles CT, Kellam P, Allday MJ. 2016a. Epstein-Barr virus nuclear protein EBNA3C directly induces expression of AID and somatic mutations in B cells. The Journal of Experimental Medicine 213:921–928. doi:10.1084/jem.20160120.
27. Kalchschmidt JS, Gillman ACT, Paschos K, Bazot Q, Kempkes B, Allday MJ. 2016b. EBNA3C Directs Recruitment of RBPJ (CBF1) to Chromatin during the Process of Gene Repression in EBV Infected B Cells. PLoS Pathogens 12:e1005383. doi:10.1371/journal.ppat.1005383.
28. Kempkes B, Ling PD. 2015. EBNA2 and Its Coactivator EBNA-LP. Current Topics in Microbiology and Immunology 391:35–59. doi:10.1007/978-3-319-22834-1_2.
29. Kempkes B, Spitkovsky D, Jansen-Dürr P, Ellwart JW, Kremmer E, Delecluse HJ, Rottenberger C, Bornkamm GW, Hammerschmidt W. 1995. B-cell proliferation and induction of early G1-regulating proteins by Epstein-Barr virus mutants conditional for EBNA2. The EMBO Journal 14:88–96.
30. Khan A, Zhang X. 2016. dbSUPER: a database of super-enhancers in mouse and human genome. Nucleic Acids Research 44:D164–D171. doi:10.1093/nar/gkv1002.
31. Koralov SB, Muljo SA, Galler GR, Krek A, Chakraborty T, Kanellopoulou C, Jensen K, Cobb BS, Merkenschlager M, Rajewsky N, Rajewsky K. 2008. Dicer ablation affects antibody diversity and cell survival in the B lymphocyte lineage. Cell 132:860–874. doi:10.1016/j.cell.2008.02.020.
32. Küçük C, Hu X, Jiang B, Klinkebiel D, Geng H, Gong Q, Bouska A, Iqbal J, Gaulard P, McKeithan TW, Chan WC. 2015. Global promoter methylation analysis reveals novel candidate tumor suppressor genes in natural killer cell lymphoma. Clinical Cancer Research 21:1699–1711. doi:10.1158/1078-0432.CCR-14-1216.
33. Le Roux A, Kerdiles B, Walls D, Dedieu JF, Perricaudet M. 1994. The Epstein-Barr virus determined nuclear antigens EBNA-3A,-3B, and-3C repress EBNA-2-mediated transactivation of the viral terminal protein 1 gene promoter. Virology 205:596–602. doi:10.1006/viro.1994.1687.
34. Ling PD, Hsieh JJ, Ruf IK, Rawlins DR, Hayward SD. 1994. EBNA-2 upregulation of Epstein-Barr virus latency promoters and the cellular CD23 promoter utilizes a common targeting intermediate, CBF1. Journal of Virology 68:5375–5383.
35. Maier S, Staffler G, Hartmann A, Höck J, Henning K, Grabusic K, Mailhammer R, Hoffmann R, Wilmanns M, Lang R, Mages J, Kempkes B. 2006. Cellular target genes of Epstein-Barr virus nuclear antigen 2. Journal of Virology 80:9761–9771. doi:10.1128/JVI.00665-06.
36. Maruo S, Johannsen E, Illanes D, Cooper A, Kieff E. 2003. Epstein-Barr Virus nuclear protein EBNA3A is critical for maintaining lymphoblastoid cell line growth. Journal of Virology 77:10437–10447. doi:10.1128/JVI.77.19.10437-10447.2003.
37. Maruo S, Wu Y, Ishikawa S, Kanda T, Iwakiri D, Takada K. 2006. Epstein-Barr virus nuclear protein EBNA3C is required for cell cycle progression and growth maintenance of lymphoblastoid cells. PNAS 103:19500–19505. doi:10.1073/pnas.0604919104.
38. Mbulaiteye SM, Pullarkat ST, Nathwani BN, Weiss LM, Rao N, Emmanuel B, Lynch CF, Hernandez B, Neppalli V, Hawes D, Cockburn MG, Kim A, Williams M, Altekruse S, Bhatia K, Goodman MT, Cozen W. 2014. Epstein-Barr virus patterns in US Burkitt lymphoma tumors from the SEER residual tissue repository during 1979-2009. APMIS 122:5–15. doi:10.1111/apm.12078.
39. McClellan MJ, Khasnis S, Wood CD, Palermo RD, Schlick SN, Kanhere AS, Jenner RG, West MJ. 2012. Downregulation of integrin receptor-signaling genes by Epstein-Barr virus EBNA 3C via promoter-proximal and-distal binding elements. Journal of Virology 86:5165–5178. doi:10.1128/JVI.07161-11.
40. McClellan MJ, Wood CD, Ojeniyi O, Cooper TJ, Kanhere A, Arvey A, Webb HM, Palermo RD, Harth-Hertle ML, Kempkes B, Jenner RG, West MJ. 2013. Modulation of enhancer looping and differential gene targeting by Epstein-Barr virus transcription factors directs cellular reprogramming. PLoS Pathogens 9:e1003636. doi:10.1371/journal.ppat.1003636.
41. Mifsud B, Tavares-Cadete F, Young AN, Sugar R, Schoenfelder S, Ferreira L, Wingett SW, Andrews S, Grey W, Ewels PA, Herman B, Happe S, Higgs A, LeProust E, Follows GA, Fraser P, Luscombe NM, Osborne CS. 2015. Mapping long-range promoter contacts in human cells with high-resolution capture Hi-C. Nature Genetics 47: 598–606. doi:10.1038/ng.3286.
42. Naumova N, Smith EM, Zhan Y, Dekker J. 2012. Analysis of long-range chromatin interactions using Chromosome Conformation Capture. Methods 58:192–203. doi:10.1016/j.ymeth.2012.07.022.
43. Neri A, Barriga F, Knowles DM, Magrath IT, Dalla-Favera R. 1988. Different regions of the immunoglobulin heavy-chain locus are involved in chromosomal translocations in distinct pathogenetic forms of Burkitt lymphoma. PNAS 85:2748–2752. doi:10.1073/pnas.85.8.2748.
44. O’Hurley G, Busch C, Fagerberg L, Hallström BM, Stadler C, Tolf A, Lundberg E, Schwenk JM, Jirström K, Bjartell A, Gallagher WM, Uhlén M, Pontén F. 2015. Analysis of the human prostate-specific proteome defined by transcriptomics and antibody-based profiling identifies TMEM79 and ACOXL as two putative, diagnostic markers in prostate cancer. PLoS One 10:e0133449. doi:10.1371/journal.pone.0133449.
45. Paschos K, Parker GA, Watanatanasup E, White RE, Allday MJ. 2012. BIM promoter directly targeted by EBNA3C in polycomb-mediated repression by EBV. Nucleic Acids Research 40:7233–7246. doi:10.1093/nar/gks391.
46. Paschos K, Smith P, Anderton E, Middeldorp JM, White RE, Allday MJ. 2009. Epstein-barr virus latency in B cells leads to epigenetic repression and CpG methylation of the tumour suppressor gene Bim. PLoS Pathogens 5: e1000492. doi:10.1371/journal.ppat.1000492.
47. Pelicci PG, Knowles DM, Magrath I, Dalla-Favera R. 1986. Chromosomal breakpoints and structural alterations of the c-myc locus differ in endemic and sporadic forms of Burkitt lymphoma. PNAS 83:2984–2988. doi:10.1073/pnas.83.9.2984.
48. Pomerantz MM, Ahmadiyeh N, Jia L, Herman P, Verzi MP, Doddapaneni H, Beckwith CA, Chan JA, Hills A, Davis M, Yao K, Kehoe SM, Lenz HJ, Haiman CA, Yan C, Henderson BE, Frenkel B, Barretina J, Bass A, Tabernero J, et al. 2009. The 8q24 cancer risk variant rs6983267 shows long-range interaction with MYC in colorectal cancer. Nature Genetics 41:882–884. doi:10.1038/ng.403.
49. Robbiani DF, Bothmer A, Callen E, Reina-San-Martin B, Dorsett Y, Difilippantonio S, Bolland DJ, Chen HT, Corcoran AE, Nussenzweig A, Nussenzweig MC. 2008. AID is required for the chromosomal breaks in c-myc that lead to c-myc/IgH translocations. Cell 135:1028–1038. doi:10.1016/j.cell.2008.09.062.
50. Robertson ES, Grossman S, Johannsen E, Miller C, Lin J, Tomkinson B, Kieff E. 1995. Epstein-Barr virus nuclear protein 3C modulates transcription through interaction with the sequence-specific DNA-binding protein J kappa. Journal of Virology 69:3108–3116.
51. Robertson ES, Lin J, Kieff E. 1996. The amino-terminal domains of Epstein-Barr virus nuclear proteins 3A, 3B, and 3C interact with RBPJ(kappa). Journal of Virology 70:3068–3074.
52. Schmidt SCS, Jiang S, Zhou H, Willox B, Holthaus AM, Kharchenko PV, Johannsen EC, Kieff E, Zhao B. 2015. Epstein–Barr virus nuclear antigen 3A partially coincides with EBNA3C genome-wide and is tethered to DNA through BATF complexes. PNAS 112:554–559. doi:10.1073/pnas.1422580112.
53. Shi J, Whyte WA, Zepeda-Mendoza CJ, Milazzo JP, Shen C, Roe JS, Minder JL, Mercan F, Wang E, Eckersley-Maslin MA, Campbell AE, Kawaoka S, Shareef S, Zhu Z, Kendall J, Muhar M, Haslinger C, Yu M, Roeder RG, Wigler MH, et al. 2013. Role of SWI/SNF in acute leukemia maintenance and enhancer-mediated Myc regulation. Genes & Development 27:2648–2662. doi:10.1101/gad.232710.113.
54. Shiramizu B, Barriga F, Neequaye J, Jafri A, Dalla-Favera R, Neri A, Guttierez M, Levine P, Magrath I. 1991. Patterns of chromosomal breakpoint locations in Burkitt’s lymphoma: relevance to geography and Epstein-Barr virus association. Blood 77:1516–1526.
55. Skalska L, White RE, Franz M, Ruhmann M, Allday MJ. 2010. Epigenetic repression of p16(INK4A) by latent Epstein-Barr virus requires the interaction of EBNA3A and EBNA3C with CtBP. PLoS Pathogens 6:e1000951. doi:10.1371/journal.ppat.1000951.
56. Speedy HE, Di Bernardo MC, Sava GP, Dyer MJ, Holroyd A, Wang Y, Sunter NJ, Mansouri L, Juliusson G, Smedby KE, Roos G, Jayne S, Majid A, Dearden C, Hall AG, Mainou-Fowler T, Jackson GH, Summerfield G, Harris RJ, Pettitt AR, et al. 2014. A genome-wide association study identifies multiple susceptibility loci for chronic lymphocytic leukemia. Nature Genetics 46:56–60. doi:10.1038/ng.2843.
57. Spender LC, Cornish GH, Sullivan A, Farrell PJ. 2002. Expression of transcription factor AML-2 (RUNX3, CBF (alpha)-3) is induced by Epstein-Barr virus EBNA-2 and correlates with the B-cell activation phenotype. Journal of Virology 76:4919–4927. doi:10.1128/JVI.76.10.4919-4927.2002.
58. Splinter E, de Wit E, van de Werken HJ, Klous P, de Laat W. 2012. Determining long-range chromatin interactions for selected genomic sites using 4C-seq technology: from fixation to computation. Methods 58: 221–251. doi:10.1016/j.ymeth.2012.04.009.
59. Tagawa H, Karnan S, Suzuki R, Matsuo K, Zhang X, Ota A, Morishima Y, Nakamura S, Seto M. 2005. Genome-wide array-based CGH for mantle cell lymphoma: identification of homozygous deletions of the proapoptotic gene BIM. Oncogene 24:1348–1358. doi:10.1038/sj.onc.1208300.
60. Thorley-Lawson DA, Allday MJ. 2008. The curious case of the tumour virus: 50 years of Burkitt’s lymphoma. Nature Reviews Microbiology 6:913–924. doi:10.1038/nrmicro2015.
61. Thorley-Lawson DA, Babcock GJ. 1999. A model for persistent infection with Epstein-Barr virus: the stealth virus of human B cells. Life Sciences 65:1433–1453. doi:10.1016/S0024-3205(99)00214-3.
62. Tomkinson B, Kieff E. 1992. Use of second-site homologous recombination to demonstrate that Epstein-Barr virus nuclear protein 3B is not important for lymphocyte infection or growth transformation in vitro. Journal of Virology 66:2893–2903.
63. Tomkinson B, Robertson E, Kieff E. 1993. Epstein-Barr virus nuclear proteins EBNA-3A and EBNA-3C are essential for B-lymphocyte growth transformation. Journal of Virology 67:2014–2025.
64. Tuupanen S, Turunen M, Lehtonen R, Hallikas O, Vanharanta S, Kivioja T, Björklund M, Wei G, Yan J, Niittymäki I, Mecklin JP, Järvinen H, Ristimäki A, Di-Bernardo M, East P, Carvajal-Carmona L, Houlston RS, Tomlinson I, Palin K, Ukkonen E, et al. 2009. The common colorectal cancer predisposition SNP rs6983267 at chromosome 8q24 confers potential to enhanced Wnt signaling. Nature Genetics 41:885–890. doi:10.1038/ng.406.
65. Ventura A, Young AG, Winslow MM, Lintault L, Meissner A, Erkeland SJ, Newman J, Bronson RT, Crowley D, Stone JR, Jaenisch R, Sharp PA, Jacks T. 2008. Targeted deletion reveals essential and overlapping functions of the miR-17 through 92 family of miRNA clusters. Cell 132:875–886. doi:10.1016/j.cell.2008.02.019.
66. Waltzer L, Logeat F, Brou C, Israel A, Sergeant A, Manet E. 1994. The human J kappa recombination signal sequence binding protein (RBP-J kappa) targets the Epstein-Barr virus EBNA2 protein to its DNA responsive elements. The EMBO Journal 13:5633–5638.
67. Waltzer L, Perricaudet M, Sergeant A, Manet E. 1996. Epstein-Barr virus EBNA3A and EBNA3C proteins both repress RBP-J kappa-EBNA2-activated transcription by inhibiting the binding of RBP-J kappa to DNA. Journal of Virology 70:5909–5915.
68. Wang E, Kawaoka S, Roe J-S, Shi J, Hohmann AF, Xu Y, Bhagwat AS, Suzuki Y, Kinney JB, Vakoc CR. 2015. The transcriptional cofactor TRIM33 prevents apoptosis in B lymphoblastic leukemia by deactivating a single enhancer. eLife 4:e06377. doi:10.7554/eLife.06377.
69. White RE, Groves IJ, Turro E, Yee J, Kremmer E, Allday MJ. 2010. Extensive co-operation between the Epstein-Barr virus EBNA3 proteins in the manipulation of host gene expression and epigenetic chromatin modification. PLoS One 5:e13979. doi:10.1371/journal.pone.0013979.
70. White RE, Rämer PC, Naresh KN, Meixlsperger S, Pinaud L, Rooney C, Savoldo B, Coutinho R, Bödör C, Gribben J, Ibrahim HA, Bower M, Nourse JP, Gandhi MK, Middeldorp J, Cader FZ, Murray P, Münz C, Allday MJ. 2012. EBNA3B-deficient EBV promotes B cell lymphomagenesis in humanized mice and is found in human tumors. Journal of Clinical Investigation 122:1487–1502. doi:10.1172/JCI58092.
71. Whyte WA, Orlando DA, Hnisz D, Abraham BJ, Lin CY, Kagey MH, Rahl PB, Lee TI, Young RA. 2013. Master transcription factors and mediator establish super-enhancers at key cell identity genes. Cell 153:307–319. doi:10.1016/j.cell.2013.03.035.
72. Wu DY, Kalpana GV, Goff SP, Schubach WH. 1996. Epstein-Barr virus nuclear protein 2 (EBNA2) binds to a component of the human SNF-SWI complex, hSNF5/Ini1. Journal of Virology 70:6020–6028.
73. Yochum GS. 2011. Multiple Wnt/ß-catenin responsive enhancers align with the MYC promoter through long-range chromatin loops. PLoS One 6:e18966. doi:10.1371/journal.pone.0018966.
74. Zhang X, Choi PS, Francis JM, Imielinski M, Watanabe H, Cherniack AD, Meyerson M. 2016. Identification of focally amplified lineage-specific super-enhancers in human epithelial cancers. Nature Genetics 48:176–182. doi:10.1038/ng.3470.
75. Zhao B, Mar JC, Maruo S, Lee S, Gewurz BE, Johannsen E, Holton K, Rubio R, Takada K, Quackenbush J, Kieff E. 2011a. Epstein-Barr virus nuclear antigen 3C regulated genes in lymphoblastoid cell lines. PNAS 108:337–342. doi:10.1073/pnas.1017419108.
76. Zhao B, Marshall DR, Sample CE. 1996. A conserved domain of the Epstein-Barr virus nuclear antigens 3A and 3C binds to a discrete domain of Jkappa. Journal of Virology 70:4228–4236.
77. Zhao B, Maruo S, Cooper A. R., Chase M, Johannsen E, Kieff E, Cahir-McFarland E. 2006. RNAs induced by Epstein-Barr virus nuclear antigen 2 in lymphoblastoid cell lines. PNAS 103:1900–1905. doi:10.1073/pnas.0510612103.
78. Zhao B, Zou J, Wang H, Johannsen E, Peng C.-W., Quackenbush J, Mar JC, Morton CC, Freedman ML, Blacklow SC, Aster JC, Bernstein BE, Kieff E. 2011b. Epstein-Barr virus exploits intrinsic B-lymphocyte transcription programs to achieve immortal cell growth. PNAS 108:14902–14907. doi:10.1073/pnas.1108892108.
79. Zhou H, Schmidt SC, Jiang S, Willox B, Bernhardt K, Liang J, Johannsen EC, Kharchenko P, Gewurz BE, Kieff E, Zhao B. 2015. Epstein-Barr virus oncoprotein super-enhancers control B cell growth. Cell Host & Microbe 17: 205–216. doi:10.1016/j.chom.2014.12.013