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. 1989 Mar 11;17(5):1989–2003. doi: 10.1093/nar/17.5.1989

Epstein-Barr virus episome-based promoter function in human myeloid cells.

C A Hauer 1, R R Getty 1, M L Tykocinski 1
PMCID: PMC317538  PMID: 2538801

Abstract

Epstein-Barr virus (EBV) episomal replicons offer an expeditious means for amplifying transfected genes in human cells. A panel of EBV episomes was constructed to assess the relative utility of five distinct eukaryotic promoter elements for high level and inducible gene expression in stably transfected human myeloid leukemia cells. The Rous sarcoma virus 3' long terminal repeat (LTR) was most highly suited for EBV episome-based gene expression, whereas the lymphopapilloma virus and the SV40 early regulatory elements exhibited substantially lower activities. Chemically responsive promoter elements, such as the SV40 early, human metallothionein IIA and rat GRP78 gene promoters, retained their inducibility when EBV episome-based. Differences in gene expression obtained with the episomes reflected differential promoter activity rather than significant variations in episome copy numbers per cell. These observations provide guidelines for the optimal design of EBV episomal expression vectors for human expression work.

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Selected References

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  1. Chiu R., Imagawa M., Imbra R. J., Bockoven J. R., Karin M. Multiple cis- and trans-acting elements mediate the transcriptional response to phorbol esters. Nature. 1987 Oct 15;329(6140):648–651. doi: 10.1038/329648a0. [DOI] [PubMed] [Google Scholar]
  2. Chu G., Hayakawa H., Berg P. Electroporation for the efficient transfection of mammalian cells with DNA. Nucleic Acids Res. 1987 Feb 11;15(3):1311–1326. doi: 10.1093/nar/15.3.1311. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Ciliberto G., Dente L., Cortese R. Cell-specific expression of a transfected human alpha 1-antitrypsin gene. Cell. 1985 Jun;41(2):531–540. doi: 10.1016/s0092-8674(85)80026-x. [DOI] [PubMed] [Google Scholar]
  4. Drinkwater N. R., Klinedinst D. K. Chemically induced mutagenesis in a shuttle vector with a low-background mutant frequency. Proc Natl Acad Sci U S A. 1986 May;83(10):3402–3406. doi: 10.1073/pnas.83.10.3402. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Gorman C. M., Merlino G. T., Willingham M. C., Pastan I., Howard B. H. The Rous sarcoma virus long terminal repeat is a strong promoter when introduced into a variety of eukaryotic cells by DNA-mediated transfection. Proc Natl Acad Sci U S A. 1982 Nov;79(22):6777–6781. doi: 10.1073/pnas.79.22.6777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Gritz L., Davies J. Plasmid-encoded hygromycin B resistance: the sequence of hygromycin B phosphotransferase gene and its expression in Escherichia coli and Saccharomyces cerevisiae. Gene. 1983 Nov;25(2-3):179–188. doi: 10.1016/0378-1119(83)90223-8. [DOI] [PubMed] [Google Scholar]
  8. Harris P., Ralph P. Human leukemic models of myelomonocytic development: a review of the HL-60 and U937 cell lines. J Leukoc Biol. 1985 Apr;37(4):407–422. doi: 10.1002/jlb.37.4.407. [DOI] [PubMed] [Google Scholar]
  9. Haslinger A., Karin M. Upstream promoter element of the human metallothionein-IIA gene can act like an enhancer element. Proc Natl Acad Sci U S A. 1985 Dec;82(24):8572–8576. doi: 10.1073/pnas.82.24.8572. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hirt B. Selective extraction of polyoma DNA from infected mouse cell cultures. J Mol Biol. 1967 Jun 14;26(2):365–369. doi: 10.1016/0022-2836(67)90307-5. [DOI] [PubMed] [Google Scholar]
  11. Imbra R. J., Karin M. Phorbol ester induces the transcriptional stimulatory activity of the SV40 enhancer. Nature. 1986 Oct 9;323(6088):555–558. doi: 10.1038/323555a0. [DOI] [PubMed] [Google Scholar]
  12. Karin M., Haslinger A., Holtgreve H., Cathala G., Slater E., Baxter J. D. Activation of a heterologous promoter in response to dexamethasone and cadmium by metallothionein gene 5'-flanking DNA. Cell. 1984 Feb;36(2):371–379. doi: 10.1016/0092-8674(84)90230-7. [DOI] [PubMed] [Google Scholar]
  13. Kioussis D., Wilson F., Daniels C., Leveton C., Taverne J., Playfair J. H. Expression and rescuing of a cloned human tumour necrosis factor gene using an EBV-based shuttle cosmid vector. EMBO J. 1987 Feb;6(2):355–361. doi: 10.1002/j.1460-2075.1987.tb04762.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Koeffler H. P. Human acute myeloid leukemia lines: models of leukemogenesis. Semin Hematol. 1986 Jul;23(3):223–236. [PubMed] [Google Scholar]
  15. Larrick J. W., Fischer D. G., Anderson S. J., Koren H. S. Characterization of a human macrophage-like cell line stimulated in vitro: a model of macrophage functions. J Immunol. 1980 Jul;125(1):6–12. [PubMed] [Google Scholar]
  16. Larsson L. G., Ivhed I., Gidlund M., Pettersson U., Vennström B., Nilsson K. Phorbol ester-induced terminal differentiation is inhibited in human U-937 monoblastic cells expressing a v-myc oncogene. Proc Natl Acad Sci U S A. 1988 Apr;85(8):2638–2642. doi: 10.1073/pnas.85.8.2638. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lin A. Y., Chang S. C., Lee A. S. A calcium ionophore-inducible cellular promoter is highly active and has enhancerlike properties. Mol Cell Biol. 1986 Apr;6(4):1235–1243. doi: 10.1128/mcb.6.4.1235. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lupton S., Levine A. J. Mapping genetic elements of Epstein-Barr virus that facilitate extrachromosomal persistence of Epstein-Barr virus-derived plasmids in human cells. Mol Cell Biol. 1985 Oct;5(10):2533–2542. doi: 10.1128/mcb.5.10.2533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Maio J. J., Brown F. L. Regulation of expression driven by human immunodeficiency virus type 1 and human T-cell leukemia virus type I long terminal repeats in pluripotential human embryonic cells. J Virol. 1988 Apr;62(4):1398–1407. doi: 10.1128/jvi.62.4.1398-1407.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Margolskee R. F., Kavathas P., Berg P. Epstein-Barr virus shuttle vector for stable episomal replication of cDNA expression libraries in human cells. Mol Cell Biol. 1988 Jul;8(7):2837–2847. doi: 10.1128/mcb.8.7.2837. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Mecsas J., Sugden B. Replication of plasmids derived from bovine papilloma virus type 1 and Epstein-Barr virus in cells in culture. Annu Rev Cell Biol. 1987;3:87–108. doi: 10.1146/annurev.cb.03.110187.000511. [DOI] [PubMed] [Google Scholar]
  22. Miksicek R., Heber A., Schmid W., Danesch U., Posseckert G., Beato M., Schütz G. Glucocorticoid responsiveness of the transcriptional enhancer of Moloney murine sarcoma virus. Cell. 1986 Jul 18;46(2):283–290. doi: 10.1016/0092-8674(86)90745-2. [DOI] [PubMed] [Google Scholar]
  23. Minta J. O., Pambrun L. In vitro induction of cytologic and functional differentiation of the immature human monocytelike cell line U-937 with phorbol myristate acetate. Am J Pathol. 1985 Apr;119(1):111–126. [PMC free article] [PubMed] [Google Scholar]
  24. Mosthaf L., Pawlita M., Gruss P. A viral enhancer element specifically active in human haematopoietic cells. Nature. 1985 Jun 13;315(6020):597–600. doi: 10.1038/315597a0. [DOI] [PubMed] [Google Scholar]
  25. Petit A. J., Terpstra F. G., Miedema F. Human immunodeficiency virus infection down-regulates HLA class II expression and induces differentiation in promonocytic U937 cells. J Clin Invest. 1987 Jun;79(6):1883–1889. doi: 10.1172/JCI113032. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Razzaque A., Mizusawa H., Seidman M. M. Rearrangement and mutagenesis of a shuttle vector plasmid after passage in mammalian cells. Proc Natl Acad Sci U S A. 1983 May;80(10):3010–3014. doi: 10.1073/pnas.80.10.3010. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Reed K. C., Mann D. A. Rapid transfer of DNA from agarose gels to nylon membranes. Nucleic Acids Res. 1985 Oct 25;13(20):7207–7221. doi: 10.1093/nar/13.20.7207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Reisman D., Sugden B. trans activation of an Epstein-Barr viral transcriptional enhancer by the Epstein-Barr viral nuclear antigen 1. Mol Cell Biol. 1986 Nov;6(11):3838–3846. doi: 10.1128/mcb.6.11.3838. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Resendez E., Jr, Attenello J. W., Grafsky A., Chang C. S., Lee A. S. Calcium ionophore A23187 induces expression of glucose-regulated genes and their heterologous fusion genes. Mol Cell Biol. 1985 Jun;5(6):1212–1219. doi: 10.1128/mcb.5.6.1212. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Sandri-Goldin R. M., Goldin A. L., Levine M., Glorioso J. C. High-frequency transfer of cloned herpes simplex virus type 1 sequences to mammalian cells by protoplast fusion. Mol Cell Biol. 1981 Aug;1(8):743–752. doi: 10.1128/mcb.1.8.743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Shanahan F., Brogan M. D., Newman W., Targan S. R. K562 killing by K, IL 2-responsive NK, and T cells involves different effector cell post-binding trigger mechanisms. J Immunol. 1986 Jul 15;137(2):723–726. [PubMed] [Google Scholar]
  32. Spandidos D. A. Electric field-mediated gene transfer (electroporation) into mouse Friend and human K562 erythroleukemic cells. Gene Anal Tech. 1987 May-Jun;4(3):50–56. doi: 10.1016/0735-0651(87)90018-5. [DOI] [PubMed] [Google Scholar]
  33. Sundström C., Nilsson K. Establishment and characterization of a human histiocytic lymphoma cell line (U-937). Int J Cancer. 1976 May 15;17(5):565–577. doi: 10.1002/ijc.2910170504. [DOI] [PubMed] [Google Scholar]
  34. Toneguzzo F., Keating A., Glynn S., McDonald K. Electric field-mediated gene transfer: characterization of DNA transfer and patterns of integration in lymphoid cells. Nucleic Acids Res. 1988 Jun 24;16(12):5515–5532. doi: 10.1093/nar/16.12.5515. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Treisman R. Transient accumulation of c-fos RNA following serum stimulation requires a conserved 5' element and c-fos 3' sequences. Cell. 1985 Oct;42(3):889–902. doi: 10.1016/0092-8674(85)90285-5. [DOI] [PubMed] [Google Scholar]
  36. Tykocinski M. L., Shu H. K., Ayers D. J., Walter E. I., Getty R. R., Groger R. K., Hauer C. A., Medof M. E. Glycolipid reanchoring of T-lymphocyte surface antigen CD8 using the 3' end sequence of decay-accelerating factor's mRNA. Proc Natl Acad Sci U S A. 1988 May;85(10):3555–3559. doi: 10.1073/pnas.85.10.3555. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. 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]
  38. Young J. M., Cheadle C., Foulke J. S., Jr, Drohan W. N., Sarver N. Utilization of an Epstein-Barr virus replicon as a eukaryotic expression vector. Gene. 1988;62(2):171–185. doi: 10.1016/0378-1119(88)90556-2. [DOI] [PubMed] [Google Scholar]

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