Skip to main content
NCBI home page
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1991 Dec 25;19(24):6799–6804. doi: 10.1093/nar/19.24.6799

Role of the SV40 enhancer in the early to late shift in viral transcription.

J J Kelly 1, A G Wildeman 1
PMCID: PMC329312  PMID: 1662364

Abstract

Simian virus 40 large tumor antigen is a multifunctional protein, with two of its roles being the promotion of viral DNA replication and replication-independent activation of viral transcription. Replication leads to a shift in transcription from the early-early to the late and late-early cap sites, through mechanisms poorly understood. The viral transcription enhancer contains sequences important for both early and late transcription, and we therefore have carried out experiments to evaluate its role in these events. We find that the ability of replication to lead to a shift diminishes when early-early transcription is made increasingly stronger by multimerizing the enhancer, and suggest that replication might lead to the shift by interfering with the ability of the enhancer to direct initiation to those sites. The natural situation in the virus of having two copies of this element might represent a compromise between maximizing both T antigen expression early in infection and late gene expression after replication begins. We also show that replication-independent transcription activation by T antigen is bidirectional and involves at least in part elements to which the factor TEF-1 binds.

Full text

PDF
6799

Images in this article

6801Image
on p.6801
6801Image
on p.6801
6801Image
on p.6801
6802Image
on p.6802

Selected References

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

  1. Barrera-Saldana H., Takahashi K., Vigneron M., Wildeman A., Davidson I., Chambon P. All six GC-motifs of the SV40 early upstream element contribute to promoter activity in vivo and in vitro. EMBO J. 1985 Dec 30;4(13B):3839–3849. doi: 10.1002/j.1460-2075.1985.tb04156.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Benoist C., Chambon P. In vivo sequence requirements of the SV40 early promotor region. Nature. 1981 Mar 26;290(5804):304–310. doi: 10.1038/290304a0. [DOI] [PubMed] [Google Scholar]
  3. Brady J., Khoury G. trans Activation of the simian virus 40 late transcription unit by T-antigen. Mol Cell Biol. 1985 Jun;5(6):1391–1399. doi: 10.1128/mcb.5.6.1391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Colledge W. H., Richardson W. D., Edge M. D., Smith A. E. Extensive mutagenesis of the nuclear location signal of simian virus 40 large-T antigen. Mol Cell Biol. 1986 Nov;6(11):4136–4139. doi: 10.1128/mcb.6.11.4136. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Davidson I., Fromental C., Augereau P., Wildeman A., Zenke M., Chambon P. Cell-type specific protein binding to the enhancer of simian virus 40 in nuclear extracts. Nature. 1986 Oct 9;323(6088):544–548. doi: 10.1038/323544a0. [DOI] [PubMed] [Google Scholar]
  6. Davidson I., Xiao J. H., Rosales R., Staub A., Chambon P. The HeLa cell protein TEF-1 binds specifically and cooperatively to two SV40 enhancer motifs of unrelated sequence. Cell. 1988 Sep 23;54(7):931–942. doi: 10.1016/0092-8674(88)90108-0. [DOI] [PubMed] [Google Scholar]
  7. DePamphilis M. L. Transcriptional elements as components of eukaryotic origins of DNA replication. Cell. 1988 Mar 11;52(5):635–638. doi: 10.1016/0092-8674(88)90398-4. [DOI] [PubMed] [Google Scholar]
  8. Ernoult-Lange M., May P., Moreau P., May E. Simian virus 40 late promoter region able to initiate simian virus 40 early gene transcription in the absence of the simian virus 40 origin sequence. J Virol. 1984 Apr;50(1):163–173. doi: 10.1128/jvi.50.1.163-173.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fromental C., Kanno M., Nomiyama H., Chambon P. Cooperativity and hierarchical levels of functional organization in the SV40 enhancer. Cell. 1988 Sep 23;54(7):943–953. doi: 10.1016/0092-8674(88)90109-2. [DOI] [PubMed] [Google Scholar]
  10. Gallo G. J., Gruda M. C., Manuppello J. R., Alwine J. C. Activity of simian DNA-binding factors is altered in the presence of simian virus 40 (SV40) early proteins: characterization of factors binding to elements involved in activation of the SV40 late promoter. J Virol. 1990 Jan;64(1):173–184. doi: 10.1128/jvi.64.1.173-184.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Ghosh P. K., Lebowitz P. Simian virus 40 early mRNA's contain multiple 5' termini upstream and downstream from a Hogness-Goldberg sequence; a shift in 5' termini during the lytic cycle is mediated by large T antigen. J Virol. 1981 Oct;40(1):224–240. doi: 10.1128/jvi.40.1.224-240.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Graham F. L., van der Eb A. J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. doi: 10.1016/0042-6822(73)90341-3. [DOI] [PubMed] [Google Scholar]
  13. Gruda M. C., Alwine J. C. Simian virus 40 (SV40) T-antigen transcriptional activation mediated through the Oct/SPH region of the SV40 late promoter. J Virol. 1991 Jul;65(7):3553–3558. doi: 10.1128/jvi.65.7.3553-3558.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Haas M. W., Ramanujam P., Chandrasekharappa S. C., Subramanian K. N. Sequence requirements for activation of replication by the SV40 transcriptional promoter or enhancer elements. Virology. 1991 Jan;180(1):41–48. doi: 10.1016/0042-6822(91)90007-x. [DOI] [PubMed] [Google Scholar]
  15. Hansen U., Tenen D. G., Livingston D. M., Sharp P. A. T antigen repression of SV40 early transcription from two promoters. Cell. 1981 Dec;27(3 Pt 2):603–613. doi: 10.1016/0092-8674(81)90402-5. [DOI] [PubMed] [Google Scholar]
  16. Hartzell S. W., Byrne B. J., Subramanian K. N. The simian virus 40 minimal origin and the 72-base-pair repeat are required simultaneously for efficient induction of late gene expression with large tumor antigen. Proc Natl Acad Sci U S A. 1984 Oct;81(20):6335–6339. doi: 10.1073/pnas.81.20.6335. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Herr W., Clarke J. The SV40 enhancer is composed of multiple functional elements that can compensate for one another. Cell. 1986 May 9;45(3):461–470. doi: 10.1016/0092-8674(86)90332-6. [DOI] [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. Kanno M., Fromental C., Staub A., Ruffenach F., Davidson I., Chambon P. The SV40 TC-II(kappa B) and the related H-2Kb enhansons exhibit different cell type specific and inducible proto-enhancer activities, but the SV40 core sequence and the AP-2 binding site have no enhanson properties. EMBO J. 1989 Dec 20;8(13):4205–4214. doi: 10.1002/j.1460-2075.1989.tb08606.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Keller J. M., Alwine J. C. Analysis of an activatable promoter: sequences in the simian virus 40 late promoter required for T-antigen-mediated trans activation. Mol Cell Biol. 1985 Aug;5(8):1859–1869. doi: 10.1128/mcb.5.8.1859. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kelly J. J., Munholland J. M., Wildeman A. G. Comeasurement of simian virus 40 early and late promoter activity in HeLa and 293 cells in the presence of T antigen. J Virol. 1989 Jan;63(1):383–391. doi: 10.1128/jvi.63.1.383-391.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kumar R., Firak T. A., Schroll C. T., Subramanian K. N. Activation of gene expression is adversely affected at high multiplicities of linked simian virus 40 enhancer. Proc Natl Acad Sci U S A. 1986 May;83(10):3199–3203. doi: 10.1073/pnas.83.10.3199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Kumar R., Yoon K. P., Subramanian K. N. Replication from a proximal simian virus 40 origin is severely inhibited by multiple reiterations of the 72-base-pair repeat enhancer sequence. Mol Cell Biol. 1988 Apr;8(4):1509–1517. doi: 10.1128/mcb.8.4.1509. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Lebkowski J. S., Clancy S., Calos M. P. Simian virus 40 replication in adenovirus-transformed human cells antagonizes gene expression. Nature. 1985 Sep 12;317(6033):169–171. doi: 10.1038/317169a0. [DOI] [PubMed] [Google Scholar]
  25. Lewis E. D., Manley J. L. Repression of simian virus 40 early transcription by viral DNA replication in human 293 cells. Nature. 1985 Sep 12;317(6033):172–175. doi: 10.1038/317172a0. [DOI] [PubMed] [Google Scholar]
  26. May E., Omilli F., Ernoult-Lange M., Zenke M., Chambon P. The sequence motifs that are involved in SV40 enhancer function also control SV40 late promoter activity. Nucleic Acids Res. 1987 Mar 25;15(6):2445–2461. doi: 10.1093/nar/15.6.2445. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Myers R. M., Rio D. C., Robbins A. K., Tjian R. SV40 gene expression is modulated by the cooperative binding of T antigen to DNA. Cell. 1981 Aug;25(2):373–384. doi: 10.1016/0092-8674(81)90056-8. [DOI] [PubMed] [Google Scholar]
  28. Nomiyama H., Fromental C., Xiao J. H., Chambon P. Cell-specific activity of the constituent elements of the simian virus 40 enhancer. Proc Natl Acad Sci U S A. 1987 Nov;84(22):7881–7885. doi: 10.1073/pnas.84.22.7881. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Ondek B., Gloss L., Herr W. The SV40 enhancer contains two distinct levels of organization. Nature. 1988 May 5;333(6168):40–45. doi: 10.1038/333040a0. [DOI] [PubMed] [Google Scholar]
  30. 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]
  31. Reddy V. B., Thimmappaya B., Dhar R., Subramanian K. N., Zain B. S., Pan J., Ghosh P. K., Celma M. L., Weissman S. M. The genome of simian virus 40. Science. 1978 May 5;200(4341):494–502. doi: 10.1126/science.205947. [DOI] [PubMed] [Google Scholar]
  32. Rosales R., Vigneron M., Macchi M., Davidson I., Xiao J. H., Chambon P. In vitro binding of cell-specific and ubiquitous nuclear proteins to the octamer motif of the SV40 enhancer and related motifs present in other promoters and enhancers. EMBO J. 1987 Oct;6(10):3015–3025. doi: 10.1002/j.1460-2075.1987.tb02607.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Scheidereit C., Heguy A., Roeder R. G. Identification and purification of a human lymphoid-specific octamer-binding protein (OTF-2) that activates transcription of an immunoglobulin promoter in vitro. Cell. 1987 Dec 4;51(5):783–793. doi: 10.1016/0092-8674(87)90101-2. [DOI] [PubMed] [Google Scholar]
  34. Schirm S., Jiricny J., Schaffner W. The SV40 enhancer can be dissected into multiple segments, each with a different cell type specificity. Genes Dev. 1987 Mar;1(1):65–74. doi: 10.1101/gad.1.1.65. [DOI] [PubMed] [Google Scholar]
  35. Staudt L. M., Singh H., Sen R., Wirth T., Sharp P. A., Baltimore D. A lymphoid-specific protein binding to the octamer motif of immunoglobulin genes. Nature. 1986 Oct 16;323(6089):640–643. doi: 10.1038/323640a0. [DOI] [PubMed] [Google Scholar]
  36. Sturm R., Baumruker T., Franza B. R., Jr, Herr W. A 100-kD HeLa cell octamer binding protein (OBP100) interacts differently with two separate octamer-related sequences within the SV40 enhancer. Genes Dev. 1987 Dec;1(10):1147–1160. doi: 10.1101/gad.1.10.1147. [DOI] [PubMed] [Google Scholar]
  37. Subramanian K. N., Shenk T. Definition of the boundaries of the origin of DNA replication in simian virus 40. Nucleic Acids Res. 1978 Oct;5(10):3635–3642. doi: 10.1093/nar/5.10.3635. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. 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]
  39. Tanaka M., Grossniklaus U., Herr W., Hernandez N. Activation of the U2 snRNA promoter by the octamer motif defines a new class of RNA polymerase II enhancer elements. Genes Dev. 1988 Dec;2(12B):1764–1778. doi: 10.1101/gad.2.12b.1764. [DOI] [PubMed] [Google Scholar]
  40. Waldeck W., Sauer G. Localization of a deletion in the DNA of a biologically active simian virus 40 strain. FEBS Lett. 1976 Dec 1;71(2):313–315. doi: 10.1016/0014-5793(76)80959-3. [DOI] [PubMed] [Google Scholar]
  41. Wasylyk B., Wasylyk C., Matthes H., Wintzerith M., Chambon P. Transcription from the SV40 early-early and late-early overlapping promoters in the absence of DNA replication. EMBO J. 1983;2(9):1605–1611. doi: 10.1002/j.1460-2075.1983.tb01631.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Wildeman A. G. Transactivation of both early and late simian virus 40 promoters by large tumor antigen does not require nuclear localization of the protein. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2123–2127. doi: 10.1073/pnas.86.7.2123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. 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]
  44. Xiao J. H., Davidson I., Ferrandon D., Rosales R., Vigneron M., Macchi M., Ruffenach F., Chambon P. One cell-specific and three ubiquitous nuclear proteins bind in vitro to overlapping motifs in the domain B1 of the SV40 enhancer. EMBO J. 1987 Oct;6(10):3005–3013. doi: 10.1002/j.1460-2075.1987.tb02606.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Xiao J. H., Davidson I., Macchi M., Rosales R., Vigneron M., Staub A., Chambon P. In vitro binding of several cell-specific and ubiquitous nuclear proteins to the GT-I motif of the SV40 enhancer. Genes Dev. 1987 Oct;1(8):794–807. doi: 10.1101/gad.1.8.794. [DOI] [PubMed] [Google Scholar]
  46. Xiao J. H., Davidson I., Matthes H., Garnier J. M., Chambon P. Cloning, expression, and transcriptional properties of the human enhancer factor TEF-1. Cell. 1991 May 17;65(4):551–568. doi: 10.1016/0092-8674(91)90088-g. [DOI] [PubMed] [Google Scholar]
  47. 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]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

RESOURCES