1887

Abstract

Transcripts for the Epstein–Barr virus (EBV)-encoded nuclear antigens are initiated at the alternative promoters Wp, Cp and Qp. Although the host cell-dependent activity of Cp is regulated by DNA methylation, Qp is unmethylated independently of its activity. Because histone modifications affect the chromatin structure, we compared the levels of diacetylated histone H3, tetraacetylated histone H4 and histone H3 dimethylated on lysine 4 (H3K4me2) at Cp and Qp, in well characterized cell lines representing the major EBV latency types. We found an activity-dependent histone code: acetylated histones marked active Cp, whereas active Qp was selectively enriched both in acetylated histones and H3K4me2. We concluded that active (but not silent) Cp and Qp are located to ‘acetylation islands’ in latent, episomal EBV genomes, similar to the active chromatin domains of the human genome.

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2008-06-01
2020-01-24
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References

  1. Alazard, N., Gruffat, H., Hiriart, E., Sergeant, A. & Manet, E. ( 2003; ). Differential hyperacetylation of histones H3 and H4 upon promoter-specific recruitment of EBNA2 in Epstein-Barr virus chromatin. J Virol 77, 8166–8172.[CrossRef]
    [Google Scholar]
  2. Altiok, E., Minarovits, J., Hu, L. F., Contreras-Brodin, B., Klein, G. & Ernberg, I. ( 1992; ). Host-cell-phenotype-dependent control of the BCR2/BWR1 promoter complex regulates the expression of Epstein-Barr virus nuclear antigens 2–6. Proc Natl Acad Sci U S A 89, 905–909.[CrossRef]
    [Google Scholar]
  3. Baer, R., Bankier, A. T., Biggin, M. D., Deininger, P. L., Farrel, P. J., Gibson, T. G., Hatfull, G., Hudson, G. S., Satchwell, S. C. & other authors ( 1984; ). DNA sequence and expression of the B95–8 Epstein-Barr virus genome. Nature 310, 207–211.[CrossRef]
    [Google Scholar]
  4. Bakos, A., Banati, F., Koroknai, A., Takacs, M., Salamon, D., Minarovits-Kormuta, S., Schwarzmann, F., Wolf, H., Niller, H. H. & Minarovits, J. ( 2007; ). High resolution analysis of CpG methylation and in vivo protein-DNA interactions at the alternative Epstein-Barr virus latency promoters Qp and Cp in the nasopharyngeal carcinoma cell line C666–1. Virus Genes 35, 195–202.[CrossRef]
    [Google Scholar]
  5. Brinkman, A. B., Pennings, S. W. C., Braliou, G. G., Rietveld, L. E. G. & Stunnenberg, H. G. ( 2007; ). DNA methylation immediately adjacent to active histone marking does not silence transcription. Nucleic Acids Res 35, 801–811.[CrossRef]
    [Google Scholar]
  6. Chau, C. M. & Lieberman, P. M. ( 2004; ). Dynamic chromatin boundaries delineate a latency control region of Epstein-Barr virus. J Virol 78, 12308–12319.[CrossRef]
    [Google Scholar]
  7. Cheung, S. T., Huang, D. P., Hui, A. B. Y., Lo, K. W., Tsang, Y. S., Whitney, N. & Lee, J. C. K. ( 1999; ). Nasopharyngeal carcinoma cell line (C666–1) consistently harbouring Epstein-Barr virus. Int J Cancer 83, 121–126.[CrossRef]
    [Google Scholar]
  8. Day, L., Chau, C. M., Nebozhyn, M., Rennekamp, A. J., Showe, M. & Lieberman, P. M. ( 2007; ). Chromatin profiling of Epstein-Barr virus latency control region. J Virol 81, 6389–6401.[CrossRef]
    [Google Scholar]
  9. Dyson, P. J. & Farrell, P. J. ( 1985; ). Chromatin structure of Epstein-Barr virus. J Gen Virol 66, 1931–1940.[CrossRef]
    [Google Scholar]
  10. Ernberg, I., Falk, K., Minarovits, J., Busson, P., Tursz, T., Masucci, M. G. & Klein, G. ( 1989; ). The role of methylation in the phenotype-dependent modulation of Epstein-Barr nuclear antigen 2 and latent membrane protein genes in cells latently infected with Epstein-Barr virus. J Gen Virol 70, 2989–3002.[CrossRef]
    [Google Scholar]
  11. Fejer, G., Medveczky, M. M., Horvath, E., Lane, B., Chang, Y. & Medveczky, P. G. ( 2003; ). The latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus interacts preferentially with the terminal repeats of the genome in vivo and this complex is sufficient for episomal DNA replication. J Gen Virol 84, 1451–1462.[CrossRef]
    [Google Scholar]
  12. Fuks, F., Burgers, W. A., Brehm, A., Hughes-Davies, L. & Kouzarides, T. ( 2000; ). DNA methyltransferase Dnmt1 associates with histone deacetylase activity. Nat Genet 24, 88–91.[CrossRef]
    [Google Scholar]
  13. Gerle, B., Koroknai, A., Fejer, G., Bakos, A., Banati, F., Szenthe, K., Wolf, H., Niller, H. H., Minarovits, J. & Salamon, D. ( 2007; ). Acetylated histone H3 and H4 mark the upregulated LMP2A-promoter of Epstein-Barr virus in lymphoid cells. J Virol 81, 13242–13247.[CrossRef]
    [Google Scholar]
  14. Gregory, C. D., Rowe, M. & Rickinson, A. B. ( 1990; ). Different Epstein-Barr virus-B cell interactions in phenotypically different clones of a Burkitt's lymphoma cell line. J Gen Virol 71, 1481–1495.[CrossRef]
    [Google Scholar]
  15. Györy, I. & Minarovits, J. ( 2005; ). Epigenetic regulation of lymphoid specific gene sets. Biochem Cell Biol 83, 286–295.[CrossRef]
    [Google Scholar]
  16. Igaz, P., Fejer, G., Szalai, C., Toth, S. & Falus, A. ( 1998; ). Development of competitive mRNA PCR for the quantification of interleukin-6-responsive junB oncogene expression. Biotechniques 24, 854–860.
    [Google Scholar]
  17. Jenuwein, T. & Allis, C. D. ( 2001; ). Translating the histone code. Science 293, 1074–1080.[CrossRef]
    [Google Scholar]
  18. Jones, P. L., Veenstra, G. J., Wade, P. A., Vermaak, D., Kass, S. U., Landsberger, N., Strouboulis, J. & Wolffe, A. P. ( 1998; ). Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription. Nat Genet 19, 187–191.[CrossRef]
    [Google Scholar]
  19. Li, H. & Minarovits, J. ( 2003; ). Host cell-dependent expression of latent Epstein-Barr virus genomes: regulation by DNA methylation. Adv Cancer Res 89, 133–156.
    [Google Scholar]
  20. Liebowitz, D. ( 1998; ). Epstein-Barr virus pathogenesis. In Human Tumor Viruses, pp. 173–199. Edited by D. J. McCance. Washington, DC: ASM Press.
  21. Minarovits, J. ( 2006; ). Epigenotypes of latent herpesvirus genomes. Curr Top Microbiol Immunol 310, 61–80.
    [Google Scholar]
  22. Minarovits, J., Hu, L. F., Minarovits-Kormuta, S., Klein, G. & Ernberg, I. ( 1994; ). Sequence-specific methylation inhibits the activity of Epstein-Barr virus LMP 1 and BCR2 enhancer-promoter regions. Virology 200, 661–667.[CrossRef]
    [Google Scholar]
  23. Nan, X., Ng, H. H., Johnson, C. A., Laherty, C. D., Turner, B. M., Eisenman, R. N. & Bird, A. ( 1998; ). Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex. Nature 393, 386–389.[CrossRef]
    [Google Scholar]
  24. Ng, H. H., Jeppesen, P. & Bird, A. ( 2000; ). Active repression of methylated genes by the chromosomal protein MBD1. Mol Cell Biol 20, 1394–1406.[CrossRef]
    [Google Scholar]
  25. Niller, H. H., Salamon, D., Banati, F., Schwarzmann, F., Wolf, H. & Minarovits, J. ( 2004; ). The LCR of EBV makes Burkitt's lymphoma endemic. Trends Microbiol 12, 495–499.[CrossRef]
    [Google Scholar]
  26. Robertson, K. D., Hayward, S. D., Ling, P. D., Samid, D. & Ambinder, R. F. ( 1995; ). 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 15, 6150–6159.
    [Google Scholar]
  27. Roh, T. Y., Cuddapah, S. & Zhao, K. ( 2005; ). Active chromatin domains are defined by acetylation islands defined by genome-wide mapping. Genes Dev 19, 542–552.[CrossRef]
    [Google Scholar]
  28. Salamon, D., Takacs, M., Ujvari, D., Uhlig, J., Wolf, H., Minarovits, J. & Niller, H. H. ( 2001; ). Protein-DNA binding and CpG methylation at nucleotide resolution of latency-associated promoters Qp, Cp and LMP1p of Epstein-Barr virus. J Virol 75, 2584–2596.[CrossRef]
    [Google Scholar]
  29. Schneider, R., Bannister, A. J., Myers, F. A., Thorne, A. W., Crane-Robinson, C. & Kozuarides, T. ( 2004; ). Histone H3 lysine 4 methylation patterns in higher eukaryotic genes. Nat Cell Biol 6, 73–77.[CrossRef]
    [Google Scholar]
  30. Szekely, L., Chen, F., Teramoto, N., Ehlin-Henriksson, B., Pokrovskaja, K., Szeles, A., Manneborg-Sandlund, A., Lennette, E. T. & Klein, G. ( 1998; ). Restricted expression of Epstein-Barr virus (EBV)-encoded, growth transformation-associated antigens in an EBV- and human herpesvirus type 8-carrying body cavity lymphoma line. J Gen Virol 79, 1445–1452.
    [Google Scholar]
  31. Tao, Q., Robertson, K. D., Manns, A., Hildesheim, A. & Ambinder, R. F. ( 1998; ). The Epstein-Barr virus major latency promoter Qp is constitutively active, hypomethylated and methylation sensitive. J Virol 72, 7075–7083.
    [Google Scholar]
  32. Verdone, L., Caserta, M. & Di Mauro, E. ( 2005; ). Role of histone acetylation in the control of gene expression. Biochem Cell Biol 83, 344–353.[CrossRef]
    [Google Scholar]
  33. Weinmann, A. S. & Farnham, P. J. ( 2002; ). Identification of unknown target genes of human transcription factors using chromatin immunoprecipitation. Methods 26, 37–47.[CrossRef]
    [Google Scholar]
  34. Woisetschlaeger, M., Jin, X. W., Yandava, C. N., Fumarsky, L. A., Strominger, J. L. & Speck, S. H. ( 1991; ). Role of the Epstein-Barr virus nuclear antigen 2 in viral promoter switching during initial stages of infection. Proc Natl Acad Sci U S A 88, 3942–3946.[CrossRef]
    [Google Scholar]
  35. Zhang, Y., Fatima, N. & Dufau, M. L. ( 2005; ). Coordinated changes in DNA methylation and histone modifications regulate silencing/derepression of luteinizing hormone receptor gene transcription. Mol Cell Biol 25, 7929–7939.[CrossRef]
    [Google Scholar]
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