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. 1997 Feb;17(2):873–886. doi: 10.1128/mcb.17.2.873

Constitutive activation of Epstein-Barr virus (EBV) nuclear antigen 1 gene transcription by IRF1 and IRF2 during restricted EBV latency.

B C Schaefer 1, E Paulson 1, J L Strominger 1, S H Speck 1
PMCID: PMC231814  PMID: 9001242

Abstract

The Epstein-Barr virus (EBV) EBNA1 gene promoter active in the type I program of restricted viral latency was recently identified and shown to reside in the viral BamHI Q fragment. This promoter, Qp, is active in a wide variety of cell lines and has an architecture reminiscent of eukaryotic housekeeping gene promoters (B. C. Schaefer, J. L. Strominger, and S. H. Speck, Proc. Natl. Acad. Sci. USA 92:10565-10569, 1995; B. C. Schaefer, J. L. Strominger, and S. H. Speck, Mol. Cell. Biol. 17:364-377, 1997). Here we demonstrate by deletion analysis that the important cis-acting elements regulating Qp are clustered in a relatively small region (ca. 80 bp) surrounding the site of transcription initiation. Immediately upstream of the site of initiation is a region which is protected from DNase I digestion by crude nuclear extracts. Electrophoretic mobility shift analyses (EMSA) employing probes spanning this region demonstrated the presence of two major protein complexes. Deletion analysis of Qp demonstrated that at least one of these complexes plays an important role in Qp activity. Evidence that interferon response factor 2 (IRF2) is a major constituent of the most prominent EMSA complex and that IRF1 may be a minor component of this complex is presented. Transfections into IRF1-/-, IRF2-/-, and IRF1,2-/- fibroblasts demonstrated that absence of both IRF1 and IRF2 reduced Qp activity to approximately the same extent as mutation of the IRF-binding site in Qp, strongly implicating IRF2, and perhaps IRF1, in the regulation of Qp activity. Notably, transcription from Qp was not inducible by either alpha or gamma interferon in EBV-negative B cells but rather was shown to be constitutively activated by IRF1 and IRF2. This observation suggests that IRF1 and IRF2 have a previously unrecognized role as constitutive activators of specific genes. Additionally, data presented indicate that a protein complex containing the nonhistone architectural protein HMG-I(Y) binds to the region identified as the major transcription initiation site for Qp. This observation raises the possibility that HMG-I(Y)-induced DNA bending plays a role in the initiation of transcription from Qp.

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Selected References

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  1. Abdulkadir S. A., Krishna S., Thanos D., Maniatis T., Strominger J. L., Ono S. J. Functional roles of the transcription factor Oct-2A and the high mobility group protein I/Y in HLA-DRA gene expression. J Exp Med. 1995 Aug 1;182(2):487–500. doi: 10.1084/jem.182.2.487. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Altiok E., Minarovits J., Hu L. F., Contreras-Brodin B., Klein G., Ernberg I. 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. 1992 Feb 1;89(3):905–909. doi: 10.1073/pnas.89.3.905. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Ambinder R. F., Shah W. A., Rawlins D. R., Hayward G. S., Hayward S. D. Definition of the sequence requirements for binding of the EBNA-1 protein to its palindromic target sites in Epstein-Barr virus DNA. J Virol. 1990 May;64(5):2369–2379. doi: 10.1128/jvi.64.5.2369-2379.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Ben-Bassat H., Goldblum N., Mitrani S., Goldblum T., Yoffey J. M., Cohen M. M., Bentwich Z., Ramot B., Klein E., Klein G. Establishment in continuous culture of a new type of lymphocyte from a "Burkitt like" malignant lymphoma (line D.G.-75). Int J Cancer. 1977 Jan;19(1):27–33. doi: 10.1002/ijc.2910190105. [DOI] [PubMed] [Google Scholar]
  5. Bovolenta C., Driggers P. H., Marks M. S., Medin J. A., Politis A. D., Vogel S. N., Levy D. E., Sakaguchi K., Appella E., Coligan J. E. Molecular interactions between interferon consensus sequence binding protein and members of the interferon regulatory factor family. Proc Natl Acad Sci U S A. 1994 May 24;91(11):5046–5050. doi: 10.1073/pnas.91.11.5046. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chen F., Zou J. Z., di Renzo L., Winberg G., Hu L. F., Klein E., Klein G., Ernberg I. A subpopulation of normal B cells latently infected with Epstein-Barr virus resembles Burkitt lymphoma cells in expressing EBNA-1 but not EBNA-2 or LMP1. J Virol. 1995 Jun;69(6):3752–3758. doi: 10.1128/jvi.69.6.3752-3758.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dean F. B., O'Donnell M. Two steps to binding replication origins? DNA-protein interactions. Curr Biol. 1996 Aug 1;6(8):931–934. doi: 10.1016/s0960-9822(02)00629-2. [DOI] [PubMed] [Google Scholar]
  8. Dignam J. D., Lebovitz R. M., Roeder R. G. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983 Mar 11;11(5):1475–1489. doi: 10.1093/nar/11.5.1475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Du W., Maniatis T. The high mobility group protein HMG I(Y) can stimulate or inhibit DNA binding of distinct transcription factor ATF-2 isoforms. Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11318–11322. doi: 10.1073/pnas.91.24.11318. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. Falvo J. V., Thanos D., Maniatis T. Reversal of intrinsic DNA bends in the IFN beta gene enhancer by transcription factors and the architectural protein HMG I(Y). Cell. 1995 Dec 29;83(7):1101–1111. doi: 10.1016/0092-8674(95)90137-x. [DOI] [PubMed] [Google Scholar]
  12. Flemington E. K., Lytle J. P., Cayrol C., Borras A. M., Speck S. H. DNA-binding-defective mutants of the Epstein-Barr virus lytic switch activator Zta transactivate with altered specificities. Mol Cell Biol. 1994 May;14(5):3041–3052. doi: 10.1128/mcb.14.5.3041. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Flemington E., Speck S. H. Identification of phorbol ester response elements in the promoter of Epstein-Barr virus putative lytic switch gene BZLF1. J Virol. 1990 Mar;64(3):1217–1226. doi: 10.1128/jvi.64.3.1217-1226.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Goodbourn S., Burstein H., Maniatis T. The human beta-interferon gene enhancer is under negative control. Cell. 1986 May 23;45(4):601–610. doi: 10.1016/0092-8674(86)90292-8. [DOI] [PubMed] [Google Scholar]
  15. Goodbourn S., Maniatis T. Overlapping positive and negative regulatory domains of the human beta-interferon gene. Proc Natl Acad Sci U S A. 1988 Mar;85(5):1447–1451. doi: 10.1073/pnas.85.5.1447. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. Génin P., Bragança J., Darracq N., Doly J., Civas A. A novel PRD I and TG binding activity involved in virus-induced transcription of IFN-A genes. Nucleic Acids Res. 1995 Dec 25;23(24):5055–5063. doi: 10.1093/nar/23.24.5055. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Harada H., Fujita T., Miyamoto M., Kimura Y., Maruyama M., Furia A., Miyata T., Taniguchi T. Structurally similar but functionally distinct factors, IRF-1 and IRF-2, bind to the same regulatory elements of IFN and IFN-inducible genes. Cell. 1989 Aug 25;58(4):729–739. doi: 10.1016/0092-8674(89)90107-4. [DOI] [PubMed] [Google Scholar]
  20. Harada H., Kitagawa M., Tanaka N., Yamamoto H., Harada K., Ishihara M., Taniguchi T. Anti-oncogenic and oncogenic potentials of interferon regulatory factors-1 and -2. Science. 1993 Feb 12;259(5097):971–974. doi: 10.1126/science.8438157. [DOI] [PubMed] [Google Scholar]
  21. Jainchill J. L., Aaronson S. A., Todaro G. J. Murine sarcoma and leukemia viruses: assay using clonal lines of contact-inhibited mouse cells. J Virol. 1969 Nov;4(5):549–553. doi: 10.1128/jvi.4.5.549-553.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Jansson A., Masucci M., Rymo L. Methylation of discrete sites within the enhancer region regulates the activity of the Epstein-Barr virus BamHI W promoter in Burkitt lymphoma lines. J Virol. 1992 Jan;66(1):62–69. doi: 10.1128/jvi.66.1.62-69.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. John S., Reeves R. B., Lin J. X., Child R., Leiden J. M., Thompson C. B., Leonard W. J. Regulation of cell-type-specific interleukin-2 receptor alpha-chain gene expression: potential role of physical interactions between Elf-1, HMG-I(Y), and NF-kappa B family proteins. Mol Cell Biol. 1995 Mar;15(3):1786–1796. doi: 10.1128/mcb.15.3.1786. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Jones C. H., Hayward S. D., Rawlins D. R. Interaction of the lymphocyte-derived Epstein-Barr virus nuclear antigen EBNA-1 with its DNA-binding sites. J Virol. 1989 Jan;63(1):101–110. doi: 10.1128/jvi.63.1.101-110.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Kamijo R., Harada H., Matsuyama T., Bosland M., Gerecitano J., Shapiro D., Le J., Koh S. I., Kimura T., Green S. J. Requirement for transcription factor IRF-1 in NO synthase induction in macrophages. Science. 1994 Mar 18;263(5153):1612–1615. doi: 10.1126/science.7510419. [DOI] [PubMed] [Google Scholar]
  26. Keller A. D., Maniatis T. Identification and characterization of a novel repressor of beta-interferon gene expression. Genes Dev. 1991 May;5(5):868–879. doi: 10.1101/gad.5.5.868. [DOI] [PubMed] [Google Scholar]
  27. Kerr B. M., Lear A. L., Rowe M., Croom-Carter D., Young L. S., Rookes S. M., Gallimore P. H., Rickinson A. B. Three transcriptionally distinct forms of Epstein-Barr virus latency in somatic cell hybrids: cell phenotype dependence of virus promoter usage. Virology. 1992 Mar;187(1):189–201. doi: 10.1016/0042-6822(92)90307-b. [DOI] [PubMed] [Google Scholar]
  28. Kessler D. S., Veals S. A., Fu X. Y., Levy D. E. Interferon-alpha regulates nuclear translocation and DNA-binding affinity of ISGF3, a multimeric transcriptional activator. Genes Dev. 1990 Oct;4(10):1753–1765. doi: 10.1101/gad.4.10.1753. [DOI] [PubMed] [Google Scholar]
  29. Khanna R., Burrows S. R., Kurilla M. G., Jacob C. A., Misko I. S., Sculley T. B., Kieff E., Moss D. J. Localization of Epstein-Barr virus cytotoxic T cell epitopes using recombinant vaccinia: implications for vaccine development. J Exp Med. 1992 Jul 1;176(1):169–176. doi: 10.1084/jem.176.1.169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Kimura A., Israël A., Le Bail O., Kourilsky P. Detailed analysis of the mouse H-2Kb promoter: enhancer-like sequences and their role in the regulation of class I gene expression. Cell. 1986 Jan 31;44(2):261–272. doi: 10.1016/0092-8674(86)90760-9. [DOI] [PubMed] [Google Scholar]
  31. Klein G., Dombos L., Gothoskar B. Sensitivity of Epstein-Barr virus (EBV) producer and non-producer human lymphoblastoid cell lines to superinfection with EB-virus. Int J Cancer. 1972 Jul 15;10(1):44–57. doi: 10.1002/ijc.2910100108. [DOI] [PubMed] [Google Scholar]
  32. Klein G. Epstein-Barr virus strategy in normal and neoplastic B cells. Cell. 1994 Jun 17;77(6):791–793. doi: 10.1016/0092-8674(94)90125-2. [DOI] [PubMed] [Google Scholar]
  33. Klein G., Giovanella B., Westman A., Stehlin J. S., Mumford D. An EBV-genome-negative cell line established from an American Burkitt lymphoma; receptor characteristics. EBV infectibility and permanent conversion into EBV-positive sublines by in vitro infection. Intervirology. 1975;5(6):319–334. doi: 10.1159/000149930. [DOI] [PubMed] [Google Scholar]
  34. Krek W., Livingston D. M., Shirodkar S. Binding to DNA and the retinoblastoma gene product promoted by complex formation of different E2F family members. Science. 1993 Dec 3;262(5139):1557–1560. doi: 10.1126/science.8248803. [DOI] [PubMed] [Google Scholar]
  35. Lam E. W., La Thangue N. B. DP and E2F proteins: coordinating transcription with cell cycle progression. Curr Opin Cell Biol. 1994 Dec;6(6):859–866. doi: 10.1016/0955-0674(94)90057-4. [DOI] [PubMed] [Google Scholar]
  36. Leger H., Sock E., Renner K., Grummt F., Wegner M. Functional interaction between the POU domain protein Tst-1/Oct-6 and the high-mobility-group protein HMG-I/Y. Mol Cell Biol. 1995 Jul;15(7):3738–3747. doi: 10.1128/mcb.15.7.3738. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Lenoir G. M., Vuillaume M., Bonnardel C. The use of lymphomatous and lymphoblastoid cell lines in the study of Burkitt's lymphoma. IARC Sci Publ. 1985;(60):309–318. [PubMed] [Google Scholar]
  38. Lerman M. I., Sakai A., Yao K. T., Colburn N. H. DNA sequences in human nasopharyngeal carcinoma cells that specify susceptibility to tumor promoter-induced neoplastic transformation. Carcinogenesis. 1987 Jan;8(1):121–127. doi: 10.1093/carcin/8.1.121. [DOI] [PubMed] [Google Scholar]
  39. Levitskaya J., Coram M., Levitsky V., Imreh S., Steigerwald-Mullen P. M., Klein G., Kurilla M. G., Masucci M. G. Inhibition of antigen processing by the internal repeat region of the Epstein-Barr virus nuclear antigen-1. Nature. 1995 Jun 22;375(6533):685–688. doi: 10.1038/375685a0. [DOI] [PubMed] [Google Scholar]
  40. Levy D. E., Kessler D. S., Pine R., Reich N., Darnell J. E., Jr Interferon-induced nuclear factors that bind a shared promoter element correlate with positive and negative transcriptional control. Genes Dev. 1988 Apr;2(4):383–393. doi: 10.1101/gad.2.4.383. [DOI] [PubMed] [Google Scholar]
  41. Lozzio C. B., Lozzio B. B. Human chronic myelogenous leukemia cell-line with positive Philadelphia chromosome. Blood. 1975 Mar;45(3):321–334. [PubMed] [Google Scholar]
  42. MacGregor G. R., Caskey C. T. Construction of plasmids that express E. coli beta-galactosidase in mammalian cells. Nucleic Acids Res. 1989 Mar 25;17(6):2365–2365. doi: 10.1093/nar/17.6.2365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. 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]
  44. Matsuyama T., Kimura T., Kitagawa M., Pfeffer K., Kawakami T., Watanabe N., Kündig T. M., Amakawa R., Kishihara K., Wakeham A. Targeted disruption of IRF-1 or IRF-2 results in abnormal type I IFN gene induction and aberrant lymphocyte development. Cell. 1993 Oct 8;75(1):83–97. [PubMed] [Google Scholar]
  45. Menezes J., Leibold W., Klein G., Clements G. Establishment and characterization of an Epstein-Barr virus (EBC)-negative lymphoblastoid B cell line (BJA-B) from an exceptional, EBV-genome-negative African Burkitt's lymphoma. Biomedicine. 1975 Jul;22(4):276–284. [PubMed] [Google Scholar]
  46. Michael S. F. Mutagenesis by incorporation of a phosphorylated oligo during PCR amplification. Biotechniques. 1994 Mar;16(3):410–412. [PubMed] [Google Scholar]
  47. Min W., Pober J. S., Johnson D. R. Kinetically coordinated induction of TAP1 and HLA class I by IFN-gamma: the rapid induction of TAP1 by IFN-gamma is mediated by Stat1 alpha. J Immunol. 1996 May 1;156(9):3174–3183. [PubMed] [Google Scholar]
  48. Minarovits J., Hu L. F., Minarovits-Kormuta S., Klein G., Ernberg I. Sequence-specific methylation inhibits the activity of the Epstein-Barr virus LMP 1 and BCR2 enhancer-promoter regions. Virology. 1994 May 1;200(2):661–667. doi: 10.1006/viro.1994.1229. [DOI] [PubMed] [Google Scholar]
  49. Miyamoto M., Fujita T., Kimura Y., Maruyama M., Harada H., Sudo Y., Miyata T., Taniguchi T. Regulated expression of a gene encoding a nuclear factor, IRF-1, that specifically binds to IFN-beta gene regulatory elements. Cell. 1988 Sep 9;54(6):903–913. doi: 10.1016/s0092-8674(88)91307-4. [DOI] [PubMed] [Google Scholar]
  50. Miyashita E. M., Yang B., Lam K. M., Crawford D. H., Thorley-Lawson D. A. A novel form of Epstein-Barr virus latency in normal B cells in vivo. Cell. 1995 Feb 24;80(4):593–601. doi: 10.1016/0092-8674(95)90513-8. [DOI] [PubMed] [Google Scholar]
  51. Murray R. J., Kurilla M. G., Brooks J. M., Thomas W. A., Rowe M., Kieff E., Rickinson A. B. Identification of target antigens for the human cytotoxic T cell response to Epstein-Barr virus (EBV): implications for the immune control of EBV-positive malignancies. J Exp Med. 1992 Jul 1;176(1):157–168. doi: 10.1084/jem.176.1.157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Neish A. S., Read M. A., Thanos D., Pine R., Maniatis T., Collins T. Endothelial interferon regulatory factor 1 cooperates with NF-kappa B as a transcriptional activator of vascular cell adhesion molecule 1. Mol Cell Biol. 1995 May;15(5):2558–2569. doi: 10.1128/mcb.15.5.2558. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Nelson N., Kanno Y., Hong C., Contursi C., Fujita T., Fowlkes B. J., O'Connell E., Hu-Li J., Paul W. E., Jankovic D. Expression of IFN regulatory factor family proteins in lymphocytes. Induction of Stat-1 and IFN consensus sequence binding protein expression by T cell activation. J Immunol. 1996 May 15;156(10):3711–3720. [PubMed] [Google Scholar]
  54. Nelson N., Marks M. S., Driggers P. H., Ozato K. Interferon consensus sequence-binding protein, a member of the interferon regulatory factor family, suppresses interferon-induced gene transcription. Mol Cell Biol. 1993 Jan;13(1):588–599. doi: 10.1128/mcb.13.1.588. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Neuman E., Flemington E. K., Sellers W. R., Kaelin W. G., Jr Transcription of the E2F-1 gene is rendered cell cycle dependent by E2F DNA-binding sites within its promoter. Mol Cell Biol. 1994 Oct;14(10):6607–6615. doi: 10.1128/mcb.14.10.6607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Nonkwelo C., Skinner J., Bell A., Rickinson A., Sample J. Transcription start sites downstream of the Epstein-Barr virus (EBV) Fp promoter in early-passage Burkitt lymphoma cells define a fourth promoter for expression of the EBV EBNA-1 protein. J Virol. 1996 Jan;70(1):623–627. doi: 10.1128/jvi.70.1.623-627.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Pine R., Decker T., Kessler D. S., Levy D. E., Darnell J. E., Jr Purification and cloning of interferon-stimulated gene factor 2 (ISGF2): ISGF2 (IRF-1) can bind to the promoters of both beta interferon- and interferon-stimulated genes but is not a primary transcriptional activator of either. Mol Cell Biol. 1990 Jun;10(6):2448–2457. doi: 10.1128/mcb.10.6.2448. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Porter A. C., Chernajovsky Y., Dale T. C., Gilbert C. S., Stark G. R., Kerr I. M. Interferon response element of the human gene 6-16. EMBO J. 1988 Jan;7(1):85–92. doi: 10.1002/j.1460-2075.1988.tb02786.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Qu L., Rowe D. T. Epstein-Barr virus latent gene expression in uncultured peripheral blood lymphocytes. J Virol. 1992 Jun;66(6):3715–3724. doi: 10.1128/jvi.66.6.3715-3724.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Reeves R., Wolffe A. P. Substrate structure influences binding of the non-histone protein HMG-I(Y) to free nucleosomal DNA. Biochemistry. 1996 Apr 16;35(15):5063–5074. doi: 10.1021/bi952424p. [DOI] [PubMed] [Google Scholar]
  61. Robertson K. D., Hayward S. D., Ling P. D., Samid D., Ambinder R. F. 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 Nov;15(11):6150–6159. doi: 10.1128/mcb.15.11.6150. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Rooney C. M., Rowe M., Wallace L. E., Rickinson A. B. Epstein-Barr virus-positive Burkitt's lymphoma cells not recognized by virus-specific T-cell surveillance. Nature. 1985 Oct 17;317(6038):629–631. doi: 10.1038/317629a0. [DOI] [PubMed] [Google Scholar]
  63. Rowe D. T., Rowe M., Evan G. I., Wallace L. E., Farrell P. J., Rickinson A. B. Restricted expression of EBV latent genes and T-lymphocyte-detected membrane antigen in Burkitt's lymphoma cells. EMBO J. 1986 Oct;5(10):2599–2607. doi: 10.1002/j.1460-2075.1986.tb04540.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Ruffner H., Reis L. F., Näf D., Weissmann C. Induction of type I interferon genes and interferon-inducible genes in embryonal stem cells devoid of interferon regulatory factor 1. Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11503–11507. doi: 10.1073/pnas.90.24.11503. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Rutherford M. N., Hannigan G. E., Williams B. R. Interferon-induced binding of nuclear factors to promoter elements of the 2-5A synthetase gene. EMBO J. 1988 Mar;7(3):751–759. doi: 10.1002/j.1460-2075.1988.tb02872.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Sample J., Henson E. B., Sample C. The Epstein-Barr virus nuclear protein 1 promoter active in type I latency is autoregulated. J Virol. 1992 Aug;66(8):4654–4661. doi: 10.1128/jvi.66.8.4654-4661.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Schaefer B. C., Strominger J. L., Speck S. H. A simple reverse transcriptase PCR assay to distinguish EBNA1 gene transcripts associated with type I and II latency from those arising during induction of the viral lytic cycle. J Virol. 1996 Nov;70(11):8204–8208. doi: 10.1128/jvi.70.11.8204-8208.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Schaefer B. C., Strominger J. L., Speck S. H. Host-cell-determined methylation of specific Epstein-Barr virus promoters regulates the choice between distinct viral latency programs. Mol Cell Biol. 1997 Jan;17(1):364–377. doi: 10.1128/mcb.17.1.364. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Schaefer B. C., Strominger J. L., Speck S. H. Redefining the Epstein-Barr virus-encoded nuclear antigen EBNA-1 gene promoter and transcription initiation site in group I Burkitt lymphoma cell lines. Proc Natl Acad Sci U S A. 1995 Nov 7;92(23):10565–10569. doi: 10.1073/pnas.92.23.10565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Schaefer B. C., Strominger J. L., Speck S. H. The Epstein-Barr virus BamHI F promoter is an early lytic promoter: lack of correlation with EBNA 1 gene transcription in group 1 Burkitt's lymphoma cell lines. J Virol. 1995 Aug;69(8):5039–5047. doi: 10.1128/jvi.69.8.5039-5047.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Schaefer B. C., Woisetschlaeger M., Strominger J. L., Speck S. H. Exclusive expression of Epstein-Barr virus nuclear antigen 1 in Burkitt lymphoma arises from a third promoter, distinct from the promoters used in latently infected lymphocytes. Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6550–6554. doi: 10.1073/pnas.88.15.6550. [DOI] [PMC free article] [PubMed] [Google Scholar]
  72. Shin W. S., Hong Y. H., Peng H. B., De Caterina R., Libby P., Liao J. K. Nitric oxide attenuates vascular smooth muscle cell activation by interferon-gamma. The role of constitutive NF-kappa B activity. J Biol Chem. 1996 May 10;271(19):11317–11324. doi: 10.1074/jbc.271.19.11317. [DOI] [PubMed] [Google Scholar]
  73. Sung N. S., Wilson J., Davenport M., Sista N. D., Pagano J. S. Reciprocal regulation of the Epstein-Barr virus BamHI-F promoter by EBNA-1 and an E2F transcription factor. Mol Cell Biol. 1994 Nov;14(11):7144–7152. doi: 10.1128/mcb.14.11.7144. [DOI] [PMC free article] [PubMed] [Google Scholar]
  74. Takada K., Horinouchi K., Ono Y., Aya T., Osato T., Takahashi M., Hayasaka S. An Epstein-Barr virus-producer line Akata: establishment of the cell line and analysis of viral DNA. Virus Genes. 1991 Apr;5(2):147–156. doi: 10.1007/BF00571929. [DOI] [PubMed] [Google Scholar]
  75. Tamura T., Ishihara M., Lamphier M. S., Tanaka N., Oishi I., Aizawa S., Matsuyama T., Mak T. W., Taki S., Taniguchi T. An IRF-1-dependent pathway of DNA damage-induced apoptosis in mitogen-activated T lymphocytes. Nature. 1995 Aug 17;376(6541):596–599. doi: 10.1038/376596a0. [DOI] [PubMed] [Google Scholar]
  76. Tanaka N., Ishihara M., Kitagawa M., Harada H., Kimura T., Matsuyama T., Lamphier M. S., Aizawa S., Mak T. W., Taniguchi T. Cellular commitment to oncogene-induced transformation or apoptosis is dependent on the transcription factor IRF-1. Cell. 1994 Jun 17;77(6):829–839. doi: 10.1016/0092-8674(94)90132-5. [DOI] [PubMed] [Google Scholar]
  77. Tanaka N., Kawakami T., Taniguchi T. Recognition DNA sequences of interferon regulatory factor 1 (IRF-1) and IRF-2, regulators of cell growth and the interferon system. Mol Cell Biol. 1993 Aug;13(8):4531–4538. doi: 10.1128/mcb.13.8.4531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  78. Taniguchi T., Harada H., Lamphier M. Regulation of the interferon system and cell growth by the IRF transcription factors. J Cancer Res Clin Oncol. 1995;121(9-10):516–520. doi: 10.1007/BF01197763. [DOI] [PubMed] [Google Scholar]
  79. Thanos D., Maniatis T. Identification of the rel family members required for virus induction of the human beta interferon gene. Mol Cell Biol. 1995 Jan;15(1):152–164. doi: 10.1128/mcb.15.1.152. [DOI] [PMC free article] [PubMed] [Google Scholar]
  80. Thanos D., Maniatis T. The high mobility group protein HMG I(Y) is required for NF-kappa B-dependent virus induction of the human IFN-beta gene. Cell. 1992 Nov 27;71(5):777–789. doi: 10.1016/0092-8674(92)90554-p. [DOI] [PubMed] [Google Scholar]
  81. Thanos D., Maniatis T. Virus induction of human IFN beta gene expression requires the assembly of an enhanceosome. Cell. 1995 Dec 29;83(7):1091–1100. doi: 10.1016/0092-8674(95)90136-1. [DOI] [PubMed] [Google Scholar]
  82. Tierney R. J., Steven N., Young L. S., Rickinson A. B. Epstein-Barr virus latency in blood mononuclear cells: analysis of viral gene transcription during primary infection and in the carrier state. J Virol. 1994 Nov;68(11):7374–7385. doi: 10.1128/jvi.68.11.7374-7385.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  83. Vaughan P. S., Aziz F., van Wijnen A. J., Wu S., Harada H., Taniguchi T., Soprano K. J., Stein J. L., Stein G. S. Activation of a cell-cycle-regulated histone gene by the oncogenic transcription factor IRF-2. Nature. 1995 Sep 28;377(6547):362–365. doi: 10.1038/377362a0. [DOI] [PubMed] [Google Scholar]
  84. Veals S. A., Santa Maria T., Levy D. E. Two domains of ISGF3 gamma that mediate protein-DNA and protein-protein interactions during transcription factor assembly contribute to DNA-binding specificity. Mol Cell Biol. 1993 Jan;13(1):196–206. doi: 10.1128/mcb.13.1.196. [DOI] [PMC free article] [PubMed] [Google Scholar]
  85. Weis L., Reinberg D. Transcription by RNA polymerase II: initiator-directed formation of transcription-competent complexes. FASEB J. 1992 Nov;6(14):3300–3309. doi: 10.1096/fasebj.6.14.1426767. [DOI] [PubMed] [Google Scholar]
  86. Weiss A., Wiskocil R. L., Stobo J. D. The role of T3 surface molecules in the activation of human T cells: a two-stimulus requirement for IL 2 production reflects events occurring at a pre-translational level. J Immunol. 1984 Jul;133(1):123–128. [PubMed] [Google Scholar]
  87. Weisz A., Marx P., Sharf R., Appella E., Driggers P. H., Ozato K., Levi B. Z. Human interferon consensus sequence binding protein is a negative regulator of enhancer elements common to interferon-inducible genes. J Biol Chem. 1992 Dec 15;267(35):25589–25596. [PubMed] [Google Scholar]
  88. Whitley M. Z., Thanos D., Read M. A., Maniatis T., Collins T. A striking similarity in the organization of the E-selectin and beta interferon gene promoters. Mol Cell Biol. 1994 Oct;14(10):6464–6475. doi: 10.1128/mcb.14.10.6464. [DOI] [PMC free article] [PubMed] [Google Scholar]
  89. 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]
  90. 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]
  91. Wu L. C., Morley B. J., Campbell R. D. Cell-specific expression of the human complement protein factor B gene: evidence for the role of two distinct 5'-flanking elements. Cell. 1987 Jan 30;48(2):331–342. doi: 10.1016/0092-8674(87)90436-3. [DOI] [PubMed] [Google Scholar]
  92. Yamamoto H., Lamphier M. S., Fujita T., Taniguchi T., Harada H. The oncogenic transcription factor IRF-2 possesses a transcriptional repression and a latent activation domain. Oncogene. 1994 May;9(5):1423–1428. [PubMed] [Google Scholar]
  93. Yates J. L., Warren N., Sugden B. Stable replication of plasmids derived from Epstein-Barr virus in various mammalian cells. 1985 Feb 28-Mar 6Nature. 313(6005):812–815. doi: 10.1038/313812a0. [DOI] [PubMed] [Google Scholar]
  94. Yates J., Warren N., Reisman D., Sugden B. A cis-acting element from the Epstein-Barr viral genome that permits stable replication of recombinant plasmids in latently infected cells. Proc Natl Acad Sci U S A. 1984 Jun;81(12):3806–3810. doi: 10.1073/pnas.81.12.3806. [DOI] [PMC free article] [PubMed] [Google Scholar]
  95. Zech L., Haglund U., Nilsson K., Klein G. Characteristic chromosomal abnormalities in biopsies and lymphoid-cell lines from patients with Burkitt and non-Burkitt lymphomas. Int J Cancer. 1976 Jan 15;17(1):47–56. doi: 10.1002/ijc.2910170108. [DOI] [PubMed] [Google Scholar]
  96. van Wijnen A. J., Aziz F., Graña X., De Luca A., Desai R. K., Jaarsveld K., Last T. J., Soprano K., Giordano A., Lian J. B. Transcription of histone H4, H3, and H1 cell cycle genes: promoter factor HiNF-D contains CDC2, cyclin A, and an RB-related protein. Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12882–12886. doi: 10.1073/pnas.91.26.12882. [DOI] [PMC free article] [PubMed] [Google Scholar]
  97. van Wijnen A. J., van den Ent F. M., Lian J. B., Stein J. L., Stein G. S. Overlapping and CpG methylation-sensitive protein-DNA interactions at the histone H4 transcriptional cell cycle domain: distinctions between two human H4 gene promoters. Mol Cell Biol. 1992 Jul;12(7):3273–3287. doi: 10.1128/mcb.12.7.3273. [DOI] [PMC free article] [PubMed] [Google Scholar]

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