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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1992 Feb 1;89(3):905–909. doi: 10.1073/pnas.89.3.905

Host-cell-phenotype-dependent control of the BCR2/BWR1 promoter complex regulates the expression of Epstein-Barr virus nuclear antigens 2-6.

E Altiok 1, J Minarovits 1, L F Hu 1, B Contreras-Brodin 1, G Klein 1, I Ernberg 1
PMCID: PMC48353  PMID: 1371012

Abstract

Epstein-Barr virus nuclear antigens (EBNAs) are expressed in a cell-phenotype-dependent manner. EBNA 1 is regularly expressed in all Epstein-Barr virus-carrying cells, whereas EBNAs 2-6 are only expressed in Epstein-Barr virus-carrying cells with a lymphoblastoid phenotype including group III Burkitt lymphoma (BL) lines positive for B-cell activation markers. Transcripts are initiated at the BCR2 or exceptionally at one BWR1 promoter in lymphoblastoid cell lines and group III BL lines. In group I BL lines, nasopharyngeal carcinoma, and the somatic cell hybrids, where EBNAs 2-6 are downregulated, the BCR2/BWR1 promoter complex is inactive or switched off. Upregulation of EBNAs 2-6 in group III BL cells and in 5-azacytidine-treated group I BL cells accompanies the activation of the silent BCR2/BWR1 promoters. Activation of BCR2 parallels demethylation of at least one CpG pair in the same promoter region. The activity of BCR2/BWR1 promoter complex depends on a particular B-cell phenotype. EBNA 1 transcription must be initiated at another promoter in cells that express only EBNA 1.

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Selected References

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  1. Allen R. W., Trach K. A., Hoch J. A. Identification of the 37-kDa protein displaying a variable interaction with the erythroid cell membrane as glyceraldehyde-3-phosphate dehydrogenase. J Biol Chem. 1987 Jan 15;262(2):649–653. [PubMed] [Google Scholar]
  2. Altiok E., Klein G., Zech L., Uno M., Henriksson B. E., Battat S., Ono Y., Ernberg I. Epstein-Barr virus-transformed pro-B cells are prone to illegitimate recombination between the switch region of the mu chain gene and other chromosomes. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6333–6337. doi: 10.1073/pnas.86.16.6333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Contreras-Salazar B., Klein G., Masucci M. G. Host cell-dependent regulation of growth transformation-associated Epstein-Barr virus antigens in somatic cell hybrids. J Virol. 1989 Jun;63(6):2768–2772. doi: 10.1128/jvi.63.6.2768-2772.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dillner J., Kallin B. The Epstein-Barr virus proteins. Adv Cancer Res. 1988;50:95–158. doi: 10.1016/s0065-230x(08)60436-4. [DOI] [PubMed] [Google Scholar]
  5. Ernberg I., Falk K., Minarovits J., Busson P., Tursz T., Masucci M. G., Klein G. 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. 1989 Nov;70(Pt 11):2989–3002. doi: 10.1099/0022-1317-70-11-2989. [DOI] [PubMed] [Google Scholar]
  6. Gregory C. D., Murray R. J., Edwards C. F., Rickinson A. B. Downregulation of cell adhesion molecules LFA-3 and ICAM-1 in Epstein-Barr virus-positive Burkitt's lymphoma underlies tumor cell escape from virus-specific T cell surveillance. J Exp Med. 1988 Jun 1;167(6):1811–1824. doi: 10.1084/jem.167.6.1811. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gregory C. D., Rowe M., Rickinson A. B. Different Epstein-Barr virus-B cell interactions in phenotypically distinct clones of a Burkitt's lymphoma cell line. J Gen Virol. 1990 Jul;71(Pt 7):1481–1495. doi: 10.1099/0022-1317-71-7-1481. [DOI] [PubMed] [Google Scholar]
  8. Hu L. F., Minarovits J., Cao S. L., Contreras-Salazar B., Rymo L., Falk K., Klein G., Ernberg I. Variable expression of latent membrane protein in nasopharyngeal carcinoma can be related to methylation status of the Epstein-Barr virus BNLF-1 5'-flanking region. J Virol. 1991 Mar;65(3):1558–1567. doi: 10.1128/jvi.65.3.1558-1567.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Junker S., Pedersen S., Schreiber E., Matthias P. Extinction of an immunoglobulin kappa promoter in cell hybrids is mediated by the octamer motif and correlates with suppression of Oct-2 expression. Cell. 1990 May 4;61(3):467–474. doi: 10.1016/0092-8674(90)90528-m. [DOI] [PubMed] [Google Scholar]
  10. Masucci M. G., Contreras-Salazar B., Ragnar E., Falk K., Minarovits J., Ernberg I., Klein G. 5-Azacytidine up regulates the expression of Epstein-Barr virus nuclear antigen 2 (EBNA-2) through EBNA-6 and latent membrane protein in the Burkitt's lymphoma line rael. J Virol. 1989 Jul;63(7):3135–3141. doi: 10.1128/jvi.63.7.3135-3141.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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 Jul;72(Pt 7):1591–1599. doi: 10.1099/0022-1317-72-7-1591. [DOI] [PubMed] [Google Scholar]
  12. Sample J., Brooks L., Sample C., Young L., Rowe M., Gregory C., Rickinson A., Kieff E. Restricted Epstein-Barr virus protein expression in Burkitt lymphoma is due to a different Epstein-Barr nuclear antigen 1 transcriptional initiation site. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6343–6347. doi: 10.1073/pnas.88.14.6343. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Walls D., Perricaudet M. Novel downstream elements upregulate transcription initiated from an Epstein-Barr virus latent promoter. EMBO J. 1991 Jan;10(1):143–151. doi: 10.1002/j.1460-2075.1991.tb07930.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Woisetschlaeger M., Jin X. W., Yandava C. N., Furmanski L. A., Strominger J. L., Speck S. H. Role for the Epstein-Barr virus nuclear antigen 2 in viral promoter switching during initial stages of infection. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3942–3946. doi: 10.1073/pnas.88.9.3942. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Woisetschlaeger M., Strominger J. L., Speck S. H. Mutually exclusive use of viral promoters in Epstein-Barr virus latently infected lymphocytes. Proc Natl Acad Sci U S A. 1989 Sep;86(17):6498–6502. doi: 10.1073/pnas.86.17.6498. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Woisetschlaeger M., Yandava C. N., Furmanski L. A., Strominger J. L., Speck S. H. Promoter switching in Epstein-Barr virus during the initial stages of infection of B lymphocytes. Proc Natl Acad Sci U S A. 1990 Mar;87(5):1725–1729. doi: 10.1073/pnas.87.5.1725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Zimber-Strobl U., Suentzenich K. O., Laux G., Eick D., Cordier M., Calender A., Billaud M., Lenoir G. M., Bornkamm G. W. Epstein-Barr virus nuclear antigen 2 activates transcription of the terminal protein gene. J Virol. 1991 Jan;65(1):415–423. doi: 10.1128/jvi.65.1.415-423.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]

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