Experimental and Molecular Medicine

Korean Society for Biochemistry and Molecular Biongy (생화학분자생물학회)
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The role of promoter methylation in Epstein-Barr virus (EBV) microRNA expression in EBV-infected B cell lines

  • Kim, Do-Nyun (Research Institute of Immunobiology, Department of Medical Lifescience, College of Medicine, The Catholic University of Korea) ;
  • Song, Yoon-Jae (Department of Life Science, Kyungwon University) ;
  • Lee, Suk-Kyeong (Research Institute of Immunobiology, Department of Medical Lifescience, College of Medicine, The Catholic University of Korea)
  • Accepted : 2011.05.25
  • Published : 2011.07.31
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Abstract

Epstein-Barr virus (EBV) microRNAs (miRNAs) are expressed in EBV-associated tumors and cell lines, but the regulation mechanism of their expression is unclear yet. We investigated whether the expression of EBV miRNAs is epigenetically regulated in EBV-infected B cell lines. The expression of BART miRNAs was inversely related with the methylation level of the BART promoter at both steady-state and following 5-aza-2'-deoxycytidine treatment of the cells. The expression of BHRF1 miRNAs also became detectable with the demethylation of Cp/Wp in latency I EBV-infected cell lines. Furthermore, $in$ $vitro$ methylation of the BART and Cp promoters reduced the promoter-driven transactivation. In contrast, tricostatin A had little effect on the expression of EBV miRNA expression as well as on the BART and Cp/Wp promoters. Our results suggest that promoter methylation, but not histone acetylation, plays a role in regulation of the EBV miRNA expression in EBV-infected B cell lines.

Keywords

Acknowledgement

Grant : RNA-based development of biopharmaceutical lead molecules

Supported by : Catholic University of Korea, Ministry for Health, Welfare and Family affairs

References

  1. Abbot SD, Rowe M, Cadwallader K, Ricksten A, Gordon J, Wang F, Rymo L, Rickinson AB. Epstein-Barr virus nuclear antigen 2 induces expression of the virus-encoded latent membrane protein. J Virol 1990;64:2126-2134
  2. Al-Mozaini M, Bodelon G, Karstegl CE, Jin B, Al-Ahdal M, Farrell PJ. Epstein-Barr virus BART gene expression. J Gen Virol 2009;90:307-316 https://doi.org/10.1099/vir.0.006551-0
  3. Ambros V. The functions of animal microRNAs. Nature 2004;431:350-355 https://doi.org/10.1038/nature02871
  4. Amoroso R, Fitzsimmons L, Thomas WA, Kelly GL, Rowe M, Bell AI. Quantitative studies of Epstein-Barr virus-encoded microRNAs provide novel insights into their regulation. J Virol 2011;85:996-1010 https://doi.org/10.1128/JVI.01528-10
  5. Brooks LA, Lear AL, Young LS, Rickinson AB. Transcripts from the Epstein-Barr virus BamHI A fragment are detectable in all three forms of virus latency. J Virol 1993;67:3182-3190
  6. Bueno MJ, Perez de Castro I, Gomez de Cedron M, Santos J, Calin GA, Cigudosa JC, Croce CM, Fernández-Piqueras J, Malumbres M. Genetic and epigenetic silencing of microRNA-203 enhances ABL1 and BCR-ABL1 oncogene expression. Cancer Cell 2008;13:467-469 https://doi.org/10.1016/j.ccr.2008.05.013
  7. Cai X, Schafer A, Lu S, Bilello JP, Desrosiers RC, Edwards R, Raab-Traub N, Cullen BR. Epstein-Barr virus microRNAs are evolutionarily conserved and differentially expressed. PLoS Pathog 2006;2:e23 https://doi.org/10.1371/journal.ppat.0020023
  8. Chen H, Huang J, Wu FY, Liao G, Hutt-Fletcher L, Hayward SD. Regulation of expression of the Epstein-Barr virus BamHI-A rightward transcripts. J Virol 2005;79:1724-1733 https://doi.org/10.1128/JVI.79.3.1724-1733.2005
  9. Chen HL, Lung MM, Sham JS, Choy DT, Griffin BE, Ng MH. Transcription of BamHI-A region of the EBV genome in NPC tissues and B cells. Virology 1992;191:193-201 https://doi.org/10.1016/0042-6822(92)90181-N
  10. Chuang JC, Jones PA. Epigenetics and microRNAs. Pediatr Res 2007;61:24R-29R https://doi.org/10.1203/pdr.0b013e3180457684
  11. de Jesus O, Smith PR, Spender LC, Elgueta Karstegl C, Niller HH, Huang D, Farrell PJ. Updated Epstein-Barr virus (EBV) DNA sequence and analysis of a promoter for the BART (CST, BARF0) RNAs of EBV. J Gen Virol 2003;84:1443-1450 https://doi.org/10.1099/vir.0.19054-0
  12. Dickerson SJ, Xing Y, Robinson AR, Seaman WT, Gruffat H, Kenney SC. Methylation-dependent binding of the epsteinbarr virus BZLF1 protein to viral promoters. PLoS Pathog 2009;5:e1000356 https://doi.org/10.1371/journal.ppat.1000356
  13. Edwards RH, Marquitz AR, Raab-Traub N. Epstein-Barr virus BART microRNAs are produced from a large intron prior to splicing. J Virol 2008;82:9094-9106 https://doi.org/10.1128/JVI.00785-08
  14. Fejer G, Koroknai A, Banati F, Gyory I, Salamon D, Wolf H, Niller HH, Minarovits J. Latency type-specific distribution of epigenetic marks at the alternative promoters Cp and Qp of Epstein-Barr virus. J Gen Virol 2008;89:1364-1370 https://doi.org/10.1099/vir.0.83594-0
  15. Gilligan K, Sato H, Rajadurai P, Busson P, Young L, Rickinson A, Tursz T, Raab-Traub N. Novel transcription from the Epstein-Barr virus terminal EcoRI fragment, DIJhet, in a nasopharyngeal carcinoma. J Virol 1990;64:4948-4956
  16. Grady WM, Parkin RK, Mitchell PS, Lee JH, Kim YH, Tsuchiya KD, Washington MK, Paraskeva C, Willson JK, Kaz AM, Kroh EM, Allen A, Fritz BR, Markowitz SD, Tewari M. Epigenetic silencing of the intronic microRNA hsa-miR-342 and its host gene EVL in colorectal cancer. Oncogene 2008;27:3880-3888 https://doi.org/10.1038/onc.2008.10
  17. Grundhoff A, Sullivan CS, Ganem D. A combined computational and microarray-based approach identifies novel microRNAs encoded by human gamma-herpesviruses. RNA 2006;12:733-750 https://doi.org/10.1261/rna.2326106
  18. Guil S, Cáceres JF. The multifunctional RNA-binding protein hnRNP A1 is required for processing of miR-18a. Nat Struct Mol Biol 2007;14:591-596 https://doi.org/10.1038/nsmb1250
  19. He L, He X, Lowe SW, Hannon GJ. microRNAs join the p53 network--another piece in the tumour-suppression puzzle. Nat Rev Cancer 2007;7:819-822 https://doi.org/10.1038/nrc2232
  20. Heo I, Joo C, Cho J, Ha M, Han J, Kim VN. Lin28 mediates the terminal uridylation of let-7 precursor MicroRNA. Mol Cell 2008;32:276-284 https://doi.org/10.1016/j.molcel.2008.09.014
  21. Hitt MM, Allday MJ, Hara T, Karran L, Jones MD, Busson P, Tursz T, Ernberg I, Griffin BE. EBV gene expression in an NPC-related tumour. EMBO J 1989;8:2639-2651
  22. Jun SM, Hong YS, Seo JS, Ko YH, Yang CW, Lee SK. Viral microRNA profile in Epstein-Barr virus-associated peripheral T cell lymphoma. Br J Haematol 2008;142:320-323 https://doi.org/10.1111/j.1365-2141.2008.07186.x
  23. Jung EJ, Lee YM, Lee BL, Chang MS, Kim WH. Lytic induction and apoptosis of Epstein-Barr virus-associated gastric cancer cell line with epigenetic modifiers and ganciclovir. Cancer Lett 2007;247:77-83 https://doi.org/10.1016/j.canlet.2006.03.022
  24. Kim DN, Chae HS, Oh ST, Kang JH, Park CH, Park WS, Takada K, Lee JM, Lee WK, Lee SK. Expression of viral microRNAs in Epstein-Barr virus-associated gastric carcinoma. J Virol 2007;81:1033-1036 https://doi.org/10.1128/JVI.02271-06
  25. Kubota N, Wada K, Ito Y, Shimoyama Y, Nakamura S, Nishiyama Y, Kimura H. One-step multiplex real-time PCR assay to analyse the latency patterns of Epstein-Barr virus infection. J Virol Methods 2008;147:26-36 https://doi.org/10.1016/j.jviromet.2007.08.012
  26. Lee W, Choi HI, Kim MJ, Park SY. Depletion of mitochondrial DNA up-regulates the expression of MDR1 gene via an increase in mRNA stability. Exp Mol Med 2008;40:109-117 https://doi.org/10.3858/emm.2008.40.1.109
  27. Lee WK, Kim SM, Sim YS, Cho SG, Park SH, Kim CW, Park JG. B-lymphoblastoid cell lines from cancer patients. In Vitro Cell Dev Biol Anim 1998;34:97-100 https://doi.org/10.1007/s11626-998-0090-1
  28. Li H, Minarovits J. Host cell-dependent expression of latent Epstein-Barr virus genomes: regulation by DNA methylation. Adv Cancer Res 2003;89:133-156
  29. Michlewski G, Guil S, Semple CA, Céceres JF. Posttranscriptional regulation of miRNAs harboring conserved terminal loops. Mol Cell 2008;32:383-393 https://doi.org/10.1016/j.molcel.2008.10.013
  30. Middeldorp JM, Brink AA, van den Brule AJ, Meijer CJ. Pathogenic roles for Epstein-Barr virus (EBV) gene products in EBV-associated proliferative disorders. Crit Rev Oncol Hematol 2003;45:1-36 https://doi.org/10.1016/S1040-8428(02)00078-1
  31. Minarovits J, Minarovits-Kormuta S, Ehlin-Henriksson B, Falk K, Klein G, Ernberg I. Host cell phenotype-dependent methylation patterns of Epstein-Barr virus DNA. J Gen Virol 1991;72:1591-1599 https://doi.org/10.1099/0022-1317-72-7-1591
  32. O'Donnell KA, Wentzel EA, Zeller KI, Dang CV, Mendell JT. c-Myc-regulated microRNAs modulate E2F1 expression. Nature 2005;435:839-843 https://doi.org/10.1038/nature03677
  33. Oh ST, Cha JH, Shin DJ, Yoon SK, Lee SK. Establishment and characterization of an in vivo model for Epstein-Barr virus positive gastric carcinoma. J Med Virol 2007;79:1343-1348 https://doi.org/10.1002/jmv.20876
  34. Palii SS, Van Emburgh BO, Sankpal UT, Brown KD, Robertson KD. DNA methylation inhibitor 5-Aza-2'-deoxycytidine induces reversible genome-wide DNA damage that is distinctly influenced by DNA methyltransferases 1 and 3B. Mol Cell Biol 2008;28:752-771 https://doi.org/10.1128/MCB.01799-07
  35. Pfeffer S, Zavolan M, Grasser FA, Chien M, Russo JJ, Ju J, John B, Enright AJ, Marks D, Sander C, Tuschl T. Identification of virus-encoded microRNAs. Science 2004;304: 734-736 https://doi.org/10.1126/science.1096781
  36. Pratt ZL, Kuzembayeva M, Sengupta S, Sugden B. The microRNAs of Epstein-Barr Virus are expressed at dramatically differing levels among cell lines. Virology 2009;386: 387-397 https://doi.org/10.1016/j.virol.2009.01.006
  37. Rao PK, Kumar RM, Farkhondeh M, Baskerville S, Lodish HF. Myogenic factors that regulate expression of musclespecific microRNAs. Proc Natl Acad Sci U S A 2006;103: 8721-8726 https://doi.org/10.1073/pnas.0602831103
  38. Robertson KD, Hayward SD, Ling PD, Samid D, Ambinder RF. Transcriptional activation of the Epstein-Barr virus latency C promoter after 5-azacytidine treatment: evidence that demethylation at a single CpG site is crucial. Mol Cell Biol 1995;15:6150-6159 https://doi.org/10.1128/MCB.15.11.6150
  39. Robertson KD, Ambinder RF. Mapping promoter regions that are hypersensitive to methylation-mediated inhibition of transcription: application of the methylation cassette assay to the Epstein-Barr virus major latency promoter. J Virol 1997;71:6445-6454
  40. Saito Y, Liang G, Egger G, Friedman JM, Chuang JC, Coetzee GA, Jones PA. Specific activation of microRNA-127 with downregulation of the proto-oncogene BCL6 by chromatin-modifying drugs in human cancer cells. Cancer Cell 2006;9:435-443 https://doi.org/10.1016/j.ccr.2006.04.020
  41. Saito Y, Friedman JM, Chihara Y, Egger G, Chuang JC, Liang G. Epigenetic therapy upregulates the tumor suppressor microRNA-126 and its host gene EGFL7 in human cancer cells. Biochem Biophys Res Commun 2009;379:726-731 https://doi.org/10.1016/j.bbrc.2008.12.098
  42. Scott GK, Mattie MD, Berger CE, Benz SC, Benz CC. Rapid alteration of microRNA levels by histone deacetylase inhibition. Cancer Res 2006;66:1277-1281 https://doi.org/10.1158/0008-5472.CAN-05-3632
  43. Seo JS, Cho NY, Kim HR, Tsurumi T, Jang YS, Lee WK, Lee SK. Cell cycle arrest and lytic induction of EBV-transformed B lymphoblastoid cells by a histone deacetylase inhibitor, Trichostatin A. Oncol Rep 2008;19:93-98
  44. Smith P. Epstein-Barr virus complementary strand transcripts (CSTs/BARTs) and cancer. Semin Cancer Biol 2001;11: 469-476 https://doi.org/10.1006/scbi.2001.0414
  45. Smith PR, Gao Y, Karran L, Jones MD, Snudden D, Griffin BE. Complex nature of the major viral polyadenylated transcripts in Epstein-Barr virus-associated tumors. J Virol 1993;67:3217-3225
  46. Smith PR, de Jesus O, Turner D, Hollyoake M, Karstegl CE, Griffin BE, Karran L, Wang Y, Hayward SD, Farrell PJ. Structure and coding content of CST (BART) family RNAs of Epstein-Barr virus. J Virol 2000;74:3082-3092 https://doi.org/10.1128/JVI.74.7.3082-3092.2000
  47. Sugiura M, Imai S, Tokunaga M, Koizumi S, Uchizawa M, Okamoto K, Osato T. Transcriptional analysis of Epstein-Barr virus gene expression in EBV-positive gastric carcinoma: unique viral latency in the tumour cells. Br J Cancer 1996;74:625-631 https://doi.org/10.1038/bjc.1996.412
  48. Tao Q, Robertson KD. Stealth technology: how Epstein-Barr virus utilizes DNA methylation to cloak itself from immune detection. Clin Immunol 2003;109:53-63 https://doi.org/10.1016/S1521-6616(03)00198-0
  49. Toyota M, Suzuki H, Sasaki Y, Maruyama R, Imai K, Shinomura Y, Tokino T. Epigenetic silencing of microRNA- 34b/c and B-cell translocation gene 4 is associated with CpG island methylation in colorectal cancer. Cancer Res 2008; 68:4123-4132 https://doi.org/10.1158/0008-5472.CAN-08-0325
  50. van Beek J, Brink AA, Vervoort MB, van Zijp MJ, Meijer CJ, van den Brule AJ, Middeldorp JM. In vivo transcription of the Epstein-Barr virus (EBV) BamHI-A region without associated in vivo BARF0 protein expression in multiple EBV-associated disorders. J Gen Virol 2003;84:2647-2659 https://doi.org/10.1099/vir.0.19196-0
  51. Viswanathan SR, Daley GQ, Gregory RI. Selective blockade of microRNA processing by Lin28. Science 2008;320: 97-100 https://doi.org/10.1126/science.1154040
  52. Wei MX, Moulin JC, Decaussin G, Berger F, Ooka T. Expression and tumorigenicity of the Epstein-Barr virus BARF1 gene in human Louckes B-lymphocyte cell line. Cancer Res 1994;54:1843-1848
  53. Winter J, Jung S, Keller S, Gregory RI, Diederichs S. Many roads to maturity: microRNA biogenesis pathways and their regulation. Nat Cell Biol 2009;11:228-234 https://doi.org/10.1038/ncb0309-228
  54. Xing L, Kieff E. Epstein-Barr virus BHRF1 micro- and stable RNAs during latency III and after induction of replication. J Virol 2007;81:9967-9975 https://doi.org/10.1128/JVI.02244-06
  55. Young LS, Rickinson AB. Epstein-Barr virus: 40 years on. Nat Rev Cancer 2004;4:757-768 https://doi.org/10.1038/nrc1452

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