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. 1989 Apr;63(4):1514–1524. doi: 10.1128/jvi.63.4.1514-1524.1989

An element of the BK virus enhancer required for DNA replication.

A M Del Vecchio 1, R A Steinman 1, R P Ricciardi 1
PMCID: PMC248383  PMID: 2538642

Abstract

The human papovavirus BK virus contains three 68-base-pair (bp) repeats that act as transcriptional enhancers. An analysis of plasmids containing the BK virus origin revealed that sequences within the 68-bp enhancer are required for DNA replication as well as transcription of the early promoter in COS-1 cells. Origins with a single 68-bp repeat replicated as efficiently as did those with three repeats when transfected into COS-1 cells. Replication did not occur in the absence of enhancer sequences and could not be restored by distal placement of enhancers to enhancerless origins. However, as with simian virus 40, replication in vitro was not dependent on the presence of any enhancer sequences. Deletion analysis showed that replication of BK virus origins was dependent on the presence of the first 21 bp of the enhancer contiguous with the A-T-rich stretch of the origin. This 21-bp element is referred to as the rep element. Although in combination with rep the remaining 47 bp of the enhancer appear to increase replication by two- to fivefold, they alone are not sufficient to support replication. Deletions or insertions in the enhancer which did not alter the rep element had no major effect on replication. Site-directed mutagenesis of the Sp1-like site within the rep element, the NF1 site present in the enhancer, or the NF1 site in adjacent late-side sequences each reduced transcription by two- to fivefold, but had no effect on replication, suggesting that replication and transcription can be uncoupled.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arthur R. R., Shah K. V., Baust S. J., Santos G. W., Saral R. Association of BK viruria with hemorrhagic cystitis in recipients of bone marrow transplants. N Engl J Med. 1986 Jul 24;315(4):230–234. doi: 10.1056/NEJM198607243150405. [DOI] [PubMed] [Google Scholar]
  2. Baty D., Barrera-Saldana H. A., Everett R. D., Vigneron M., Chambon P. Mutational dissection of the 21 bp repeat region of the SV40 early promoter reveals that it contains overlapping elements of the early-early and late-early promoters. Nucleic Acids Res. 1984 Jan 25;12(2):915–932. doi: 10.1093/nar/12.2.915. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Campbell B. A., Villarreal L. P. Host species specificity of polyomavirus DNA replication is not altered by simian virus 40 72-base-pair repeats. Mol Cell Biol. 1985 Jun;5(6):1534–1537. doi: 10.1128/mcb.5.6.1534. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Caputo A., Barbanti-Brodano G., Wang E., Ricciardi R. P. Transactivation of BKV and SV40 early promoters by BKV and SV40 T-antigens. Virology. 1986 Jul 30;152(2):459–465. doi: 10.1016/0042-6822(86)90148-0. [DOI] [PubMed] [Google Scholar]
  5. Chesters P. M., Heritage J., McCance D. J. Persistence of DNA sequences of BK virus and JC virus in normal human tissues and in diseased tissues. J Infect Dis. 1983 Apr;147(4):676–684. doi: 10.1093/infdis/147.4.676. [DOI] [PubMed] [Google Scholar]
  6. DeLucia A. L., Deb S., Partin K., Tegtmeyer P. Functional interactions of the simian virus 40 core origin of replication with flanking regulatory sequences. J Virol. 1986 Jan;57(1):138–144. doi: 10.1128/jvi.57.1.138-144.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Deyerle K. L., Cassill J. A., Subramani S. Analysis of the early regulatory region of the human papovavirus BK. Virology. 1987 May;158(1):181–193. doi: 10.1016/0042-6822(87)90252-2. [DOI] [PubMed] [Google Scholar]
  8. Deyerle K. L., Subramani S. Linker scan analysis of the early regulatory region of human papovavirus BK. J Virol. 1988 Sep;62(9):3378–3387. doi: 10.1128/jvi.62.9.3378-3387.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dynan W. S., Tjian R. The promoter-specific transcription factor Sp1 binds to upstream sequences in the SV40 early promoter. Cell. 1983 Nov;35(1):79–87. doi: 10.1016/0092-8674(83)90210-6. [DOI] [PubMed] [Google Scholar]
  10. Dörries K., Loeber G., Meixensberger J. Association of polyomaviruses JC, SV40, and BK with human brain tumors. Virology. 1987 Sep;160(1):268–270. doi: 10.1016/0042-6822(87)90071-7. [DOI] [PubMed] [Google Scholar]
  11. Frisque R. J., Bream G. L., Cannella M. T. Human polyomavirus JC virus genome. J Virol. 1984 Aug;51(2):458–469. doi: 10.1128/jvi.51.2.458-469.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gardner S. D., Field A. M., Coleman D. V., Hulme B. New human papovavirus (B.K.) isolated from urine after renal transplantation. Lancet. 1971 Jun 19;1(7712):1253–1257. doi: 10.1016/s0140-6736(71)91776-4. [DOI] [PubMed] [Google Scholar]
  13. Gardner S. D. Prevalence in England of antibody to human polyomavirus (B.k.). Br Med J. 1973 Jan 13;1(5845):77–78. doi: 10.1136/bmj.1.5845.77. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gidoni D., Dynan W. S., Tjian R. Multiple specific contacts between a mammalian transcription factor and its cognate promoters. 1984 Nov 29-Dec 5Nature. 312(5993):409–413. doi: 10.1038/312409a0. [DOI] [PubMed] [Google Scholar]
  15. Gluzman Y. SV40-transformed simian cells support the replication of early SV40 mutants. Cell. 1981 Jan;23(1):175–182. doi: 10.1016/0092-8674(81)90282-8. [DOI] [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. Hertz G. Z., Mertz J. E. Bidirectional promoter elements of simian virus 40 are required for efficient replication of the viral DNA. Mol Cell Biol. 1986 Oct;6(10):3513–3522. doi: 10.1128/mcb.6.10.3513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. 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]
  19. Innis J. W., Scott W. A. DNA replication and chromatin structure of simian virus 40 insertion mutants. Mol Cell Biol. 1984 Aug;4(8):1499–1507. doi: 10.1128/mcb.4.8.1499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Jones K. A., Kadonaga J. T., Rosenfeld P. J., Kelly T. J., Tjian R. A cellular DNA-binding protein that activates eukaryotic transcription and DNA replication. Cell. 1987 Jan 16;48(1):79–89. doi: 10.1016/0092-8674(87)90358-8. [DOI] [PubMed] [Google Scholar]
  21. Jones N. C., Rigby P. W., Ziff E. B. Trans-acting protein factors and the regulation of eukaryotic transcription: lessons from studies on DNA tumor viruses. Genes Dev. 1988 Mar;2(3):267–281. doi: 10.1101/gad.2.3.267. [DOI] [PubMed] [Google Scholar]
  22. Keller J. M., Alwine J. C. Activation of the SV40 late promoter: direct effects of T antigen in the absence of viral DNA replication. Cell. 1984 Feb;36(2):381–389. doi: 10.1016/0092-8674(84)90231-9. [DOI] [PubMed] [Google Scholar]
  23. Kenney S., Natarajan V., Strike D., Khoury G., Salzman N. P. JC virus enhancer-promoter active in human brain cells. Science. 1984 Dec 14;226(4680):1337–1339. doi: 10.1126/science.6095453. [DOI] [PubMed] [Google Scholar]
  24. Kraft R., Tardiff J., Krauter K. S., Leinwand L. A. Using mini-prep plasmid DNA for sequencing double stranded templates with Sequenase. Biotechniques. 1988 Jun;6(6):544-6, 549. [PubMed] [Google Scholar]
  25. Kunkel T. A. Rapid and efficient site-specific mutagenesis without phenotypic selection. Proc Natl Acad Sci U S A. 1985 Jan;82(2):488–492. doi: 10.1073/pnas.82.2.488. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Lee-Chen G. J., Woodworth-Gutai M. Simian virus 40 DNA replication: functional organization of regulatory elements. Mol Cell Biol. 1986 Sep;6(9):3086–3093. doi: 10.1128/mcb.6.9.3086. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Li J. J., Kelly T. J. Simian virus 40 DNA replication in vitro. Proc Natl Acad Sci U S A. 1984 Nov;81(22):6973–6977. doi: 10.1073/pnas.81.22.6973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Li J. J., Peden K. W., Dixon R. A., Kelly T. Functional organization of the simian virus 40 origin of DNA replication. Mol Cell Biol. 1986 Apr;6(4):1117–1128. doi: 10.1128/mcb.6.4.1117. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Lusky M., Botchan M. Inhibition of SV40 replication in simian cells by specific pBR322 DNA sequences. Nature. 1981 Sep 3;293(5827):79–81. doi: 10.1038/293079a0. [DOI] [PubMed] [Google Scholar]
  30. Major E. O., Matsumura P. Human embryonic kidney cells: stable transformation with an origin-defective simian virus 40 DNA and use as hosts for human papovavirus replication. Mol Cell Biol. 1984 Feb;4(2):379–382. doi: 10.1128/mcb.4.2.379. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Markowitz R. B., Dynan W. S. Binding of cellular proteins to the regulatory region of BK virus DNA. J Virol. 1988 Sep;62(9):3388–3398. doi: 10.1128/jvi.62.9.3388-3398.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Mason D. H., Takemoto K. K. Complementation between BK human papovavirus and a simian virus 40 tsA mutant. J Virol. 1976 Mar;17(3):1060–1062. doi: 10.1128/jvi.17.3.1060-1062.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Milanesi G., Barbanti-Brodano G., Negrini M., Lee D., Corallini A., Caputo A., Grossi M. P., Ricciardi R. P. BK virus-plasmid expression vector that persists episomally in human cells and shuttles into Escherichia coli. Mol Cell Biol. 1984 Aug;4(8):1551–1560. doi: 10.1128/mcb.4.8.1551. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Muller W. J., Mueller C. R., Mes A. M., Hassell J. A. Polyomavirus origin for DNA replication comprises multiple genetic elements. J Virol. 1983 Sep;47(3):586–599. doi: 10.1128/jvi.47.3.586-599.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Nordheim A., Rich A. Negatively supercoiled simian virus 40 DNA contains Z-DNA segments within transcriptional enhancer sequences. Nature. 1983 Jun 23;303(5919):674–679. doi: 10.1038/303674a0. [DOI] [PubMed] [Google Scholar]
  36. Ondek B., Shepard A., Herr W. Discrete elements within the SV40 enhancer region display different cell-specific enhancer activities. EMBO J. 1987 Apr;6(4):1017–1025. doi: 10.1002/j.1460-2075.1987.tb04854.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Rosenfeld P. J., O'Neill E. A., Wides R. J., Kelly T. J. Sequence-specific interactions between cellular DNA-binding proteins and the adenovirus origin of DNA replication. Mol Cell Biol. 1987 Feb;7(2):875–886. doi: 10.1128/mcb.7.2.875. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Rosenthal N., Kress M., Gruss P., Khoury G. BK viral enhancer element and a human cellular homolog. Science. 1983 Nov 18;222(4625):749–755. doi: 10.1126/science.6314501. [DOI] [PubMed] [Google Scholar]
  39. Ryder K., DeLucia A. L., Tegtmeyer P. Binding of SV40 a protein to the BK virus origin of DNA replication. Virology. 1983 Aug;129(1):239–245. doi: 10.1016/0042-6822(83)90412-9. [DOI] [PubMed] [Google Scholar]
  40. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Schneider R., Gander I., Müller U., Mertz R., Winnacker E. L. A sensitive and rapid gel retention assay for nuclear factor I and other DNA-binding proteins in crude nuclear extracts. Nucleic Acids Res. 1986 Feb 11;14(3):1303–1317. doi: 10.1093/nar/14.3.1303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Seif I., Khoury G., Dhar R. The genome of human papovavirus BKV. Cell. 1979 Dec;18(4):963–977. doi: 10.1016/0092-8674(79)90209-5. [DOI] [PubMed] [Google Scholar]
  43. Shah K. V., Daniel R. W., Warszawski R. M. High prevalence of antibodies to BK virus, an SV40-related papovavirus, in residents of Maryland. J Infect Dis. 1973 Dec;128(6):784–787. doi: 10.1093/infdis/128.6.784. [DOI] [PubMed] [Google Scholar]
  44. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  45. Takahashi K., Vigneron M., Matthes H., Wildeman A., Zenke M., Chambon P. Requirement of stereospecific alignments for initiation from the simian virus 40 early promoter. Nature. 1986 Jan 9;319(6049):121–126. doi: 10.1038/319121a0. [DOI] [PubMed] [Google Scholar]
  46. Veldman G. M., Lupton S., Kamen R. Polyomavirus enhancer contains multiple redundant sequence elements that activate both DNA replication and gene expression. Mol Cell Biol. 1985 Apr;5(4):649–658. doi: 10.1128/mcb.5.4.649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Weiher H., König M., Gruss P. Multiple point mutations affecting the simian virus 40 enhancer. Science. 1983 Feb 11;219(4585):626–631. doi: 10.1126/science.6297005. [DOI] [PubMed] [Google Scholar]
  48. Wildeman A. G., Zenke M., Schatz C., Wintzerith M., Grundström T., Matthes H., Takahashi K., Chambon P. Specific protein binding to the simian virus 40 enhancer in vitro. Mol Cell Biol. 1986 Jun;6(6):2098–2105. doi: 10.1128/mcb.6.6.2098. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Yamaguchi M., DePamphilis M. L. DNA binding site for a factor(s) required to initiate simian virus 40 DNA replication. Proc Natl Acad Sci U S A. 1986 Mar;83(6):1646–1650. doi: 10.1073/pnas.83.6.1646. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Yang R. C., Wu R. Comparative study of papovavirus DNA: BKV(MM), BKV(WT) and SV40. Nucleic Acids Res. 1979 Oct 10;7(3):651–668. doi: 10.1093/nar/7.3.651. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Zenke M., Grundström T., Matthes H., Wintzerith M., Schatz C., Wildeman A., Chambon P. Multiple sequence motifs are involved in SV40 enhancer function. EMBO J. 1986 Feb;5(2):387–397. doi: 10.1002/j.1460-2075.1986.tb04224.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. de Villiers J., Schaffner W., Tyndall C., Lupton S., Kamen R. Polyoma virus DNA replication requires an enhancer. Nature. 1984 Nov 15;312(5991):242–246. doi: 10.1038/312242a0. [DOI] [PubMed] [Google Scholar]
  53. de Vries E., van Driel W., Tromp M., van Boom J., van der Vliet P. C. Adenovirus DNA replication in vitro: site-directed mutagenesis of the nuclear factor I binding site of the Ad2 origin. Nucleic Acids Res. 1985 Jul 11;13(13):4935–4952. doi: 10.1093/nar/13.13.4935. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. de Vries E., van Driel W., van den Heuvel S. J., van der Vliet P. C. Contactpoint analysis of the HeLa nuclear factor I recognition site reveals symmetrical binding at one side of the DNA helix. EMBO J. 1987 Jan;6(1):161–168. doi: 10.1002/j.1460-2075.1987.tb04734.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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