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. 1991 Oct;10(10):2931–2940. doi: 10.1002/j.1460-2075.1991.tb07843.x

Several different upstream promoter elements can potentiate transactivation by the BPV-1 E2 protein.

J Ham 1, N Dostatni 1, F Arnos 1, M Yaniv 1
PMCID: PMC453007  PMID: 1655407

Abstract

The enhancer and upstream promoter regions of RNA polymerase II transcribed genes modulate the rate of transcription initiation and establish specific patterns of gene expression. Both types of region consist of clusters of DNA binding sites for nuclear proteins. To determine how efficiently the same factor can activate transcription when acting as an enhancer or promoter factor, we have studied transactivation by the BPV-1 E2 protein, a papillomavirus transcriptional regulator. By cotransfecting a BPV-1 E2 expression vector and a series of reporter plasmids containing well-defined chimeric promoters we have found that whilst E2 can strongly stimulate complex promoters such as that of the HSV tk gene, it does not efficiently activate constructions containing only a TATA box and initiation site. We show that insertion of upstream promoter elements, but not of spacer DNA, between E2 binding sites and the TATA box greatly increases E2 activation. This effect was observed with more than one type of upstream promoter element, is not related to the strength of the promoter and is unlikely to result from co-operative DNA binding by E2 and the transcription factors tested. These results would suggest that E2 has the properties of an enhancer rather than promoter factor and that in certain cases promoter and enhancer factors may affect different steps in the process of transcriptional activation.

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Selected References

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

  1. Bernard B. A., Bailly C., Lenoir M. C., Darmon M., Thierry F., Yaniv M. The human papillomavirus type 18 (HPV18) E2 gene product is a repressor of the HPV18 regulatory region in human keratinocytes. J Virol. 1989 Oct;63(10):4317–4324. doi: 10.1128/jvi.63.10.4317-4324.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bienz M., Pelham H. R. Heat shock regulatory elements function as an inducible enhancer in the Xenopus hsp70 gene and when linked to a heterologous promoter. Cell. 1986 Jun 6;45(5):753–760. doi: 10.1016/0092-8674(86)90789-0. [DOI] [PubMed] [Google Scholar]
  3. Blitz I. L., Laimins L. A. The 68-kilodalton E1 protein of bovine papillomavirus is a DNA binding phosphoprotein which associates with the E2 transcriptional activator in vitro. J Virol. 1991 Feb;65(2):649–656. doi: 10.1128/jvi.65.2.649-656.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Breathnach R., Chambon P. Organization and expression of eucaryotic split genes coding for proteins. Annu Rev Biochem. 1981;50:349–383. doi: 10.1146/annurev.bi.50.070181.002025. [DOI] [PubMed] [Google Scholar]
  5. Chasman D. I., Lue N. F., Buchman A. R., LaPointe J. W., Lorch Y., Kornberg R. D. A yeast protein that influences the chromatin structure of UASG and functions as a powerful auxiliary gene activator. Genes Dev. 1990 Apr;4(4):503–514. doi: 10.1101/gad.4.4.503. [DOI] [PubMed] [Google Scholar]
  6. Chouard T., Blumenfeld M., Bach I., Vandekerckhove J., Cereghini S., Yaniv M. A distal dimerization domain is essential for DNA-binding by the atypical HNF1 homeodomain. Nucleic Acids Res. 1990 Oct 11;18(19):5853–5863. doi: 10.1093/nar/18.19.5853. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Courey A. J., Holtzman D. A., Jackson S. P., Tjian R. Synergistic activation by the glutamine-rich domains of human transcription factor Sp1. Cell. 1989 Dec 1;59(5):827–836. doi: 10.1016/0092-8674(89)90606-5. [DOI] [PubMed] [Google Scholar]
  8. Dostatni N., Thierry F., Yaniv M. A dimer of BPV-1 E2 containing a protease resistant core interacts with its DNA target. EMBO J. 1988 Dec 1;7(12):3807–3816. doi: 10.1002/j.1460-2075.1988.tb03265.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dynan W. S. Modularity in promoters and enhancers. Cell. 1989 Jul 14;58(1):1–4. doi: 10.1016/0092-8674(89)90393-0. [DOI] [PubMed] [Google Scholar]
  10. Gauthier J. M., Dostatni N., Lusky M., Yaniv M. Two DNA-bound E2 dimers are required for strong transcriptional activation and for cooperation with cellular factors in most cells. New Biol. 1991 May;3(5):498–509. [PubMed] [Google Scholar]
  11. Giri I., Yaniv M. Structural and mutational analysis of E2 trans-activating proteins of papillomaviruses reveals three distinct functional domains. EMBO J. 1988 Sep;7(9):2823–2829. doi: 10.1002/j.1460-2075.1988.tb03138.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hawley-Nelson P., Androphy E. J., Lowy D. R., Schiller J. T. The specific DNA recognition sequence of the bovine papillomavirus E2 protein is an E2-dependent enhancer. EMBO J. 1988 Feb;7(2):525–531. doi: 10.1002/j.1460-2075.1988.tb02841.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Herbomel P., Bourachot B., Yaniv M. Two distinct enhancers with different cell specificities coexist in the regulatory region of polyoma. Cell. 1984 Dec;39(3 Pt 2):653–662. doi: 10.1016/0092-8674(84)90472-0. [DOI] [PubMed] [Google Scholar]
  14. Herbomel P. Synergistic activation of eukaryotic transcription: the multiacceptor target hypothesis. New Biol. 1990 Dec;2(12):1063–1070. [PubMed] [Google Scholar]
  15. Hermonat P. L., Spalholz B. A., Howley P. M. The bovine papillomavirus P2443 promoter is E2 trans-responsive: evidence for E2 autoregulation. EMBO J. 1988 Sep;7(9):2815–2822. doi: 10.1002/j.1460-2075.1988.tb03137.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hoey T., Dynlacht B. D., Peterson M. G., Pugh B. F., Tjian R. Isolation and characterization of the Drosophila gene encoding the TATA box binding protein, TFIID. Cell. 1990 Jun 29;61(7):1179–1186. doi: 10.1016/0092-8674(90)90682-5. [DOI] [PubMed] [Google Scholar]
  17. Horikoshi M., Carey M. F., Kakidani H., Roeder R. G. Mechanism of action of a yeast activator: direct effect of GAL4 derivatives on mammalian TFIID-promoter interactions. Cell. 1988 Aug 26;54(5):665–669. doi: 10.1016/s0092-8674(88)80011-4. [DOI] [PubMed] [Google Scholar]
  18. Johnson P. F., McKnight S. L. Eukaryotic transcriptional regulatory proteins. Annu Rev Biochem. 1989;58:799–839. doi: 10.1146/annurev.bi.58.070189.004055. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Jones K. A., Yamamoto K. R., Tjian R. Two distinct transcription factors bind to the HSV thymidine kinase promoter in vitro. Cell. 1985 Sep;42(2):559–572. doi: 10.1016/0092-8674(85)90113-8. [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. Lambert P. F., Dostatni N., McBride A. A., Yaniv M., Howley P. M., Arcangioli B. Functional analysis of the papilloma virus E2 trans-activator in Saccharomyces cerevisiae. Genes Dev. 1989 Jan;3(1):38–48. doi: 10.1101/gad.3.1.38. [DOI] [PubMed] [Google Scholar]
  23. Lewin B. Commitment and activation at pol II promoters: a tail of protein-protein interactions. Cell. 1990 Jun 29;61(7):1161–1164. doi: 10.1016/0092-8674(90)90675-5. [DOI] [PubMed] [Google Scholar]
  24. Li R., Knight J. D., Jackson S. P., Tjian R., Botchan M. R. Direct interaction between Sp1 and the BPV enhancer E2 protein mediates synergistic activation of transcription. Cell. 1991 May 3;65(3):493–505. doi: 10.1016/0092-8674(91)90467-d. [DOI] [PubMed] [Google Scholar]
  25. Li R., Knight J., Bream G., Stenlund A., Botchan M. Specific recognition nucleotides and their DNA context determine the affinity of E2 protein for 17 binding sites in the BPV-1 genome. Genes Dev. 1989 Apr;3(4):510–526. doi: 10.1101/gad.3.4.510. [DOI] [PubMed] [Google Scholar]
  26. Lin Y. S., Green M. R. Mechanism of action of an acidic transcriptional activator in vitro. Cell. 1991 Mar 8;64(5):971–981. doi: 10.1016/0092-8674(91)90321-o. [DOI] [PubMed] [Google Scholar]
  27. Luckow B., Schütz G. CAT constructions with multiple unique restriction sites for the functional analysis of eukaryotic promoters and regulatory elements. Nucleic Acids Res. 1987 Jul 10;15(13):5490–5490. doi: 10.1093/nar/15.13.5490. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Maniatis T., Goodbourn S., Fischer J. A. Regulation of inducible and tissue-specific gene expression. Science. 1987 Jun 5;236(4806):1237–1245. doi: 10.1126/science.3296191. [DOI] [PubMed] [Google Scholar]
  29. McBride A. A., Byrne J. C., Howley P. M. E2 polypeptides encoded by bovine papillomavirus type 1 form dimers through the common carboxyl-terminal domain: transactivation is mediated by the conserved amino-terminal domain. Proc Natl Acad Sci U S A. 1989 Jan;86(2):510–514. doi: 10.1073/pnas.86.2.510. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. McBride A. A., Schlegel R., Howley P. M. The carboxy-terminal domain shared by the bovine papillomavirus E2 transactivator and repressor proteins contains a specific DNA binding activity. EMBO J. 1988 Feb;7(2):533–539. doi: 10.1002/j.1460-2075.1988.tb02842.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. McKnight S. L., Kingsbury R. Transcriptional control signals of a eukaryotic protein-coding gene. Science. 1982 Jul 23;217(4557):316–324. doi: 10.1126/science.6283634. [DOI] [PubMed] [Google Scholar]
  32. Mitchell P. J., Tjian R. Transcriptional regulation in mammalian cells by sequence-specific DNA binding proteins. Science. 1989 Jul 28;245(4916):371–378. doi: 10.1126/science.2667136. [DOI] [PubMed] [Google Scholar]
  33. Mohr I. J., Clark R., Sun S., Androphy E. J., MacPherson P., Botchan M. R. Targeting the E1 replication protein to the papillomavirus origin of replication by complex formation with the E2 transactivator. Science. 1990 Dec 21;250(4988):1694–1699. doi: 10.1126/science.2176744. [DOI] [PubMed] [Google Scholar]
  34. Monini P., Grossman S. R., Pepinsky B., Androphy E. J., Laimins L. A. Cooperative binding of the E2 protein of bovine papillomavirus to adjacent E2-responsive sequences. J Virol. 1991 Apr;65(4):2124–2130. doi: 10.1128/jvi.65.4.2124-2130.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Montminy M. R., Sevarino K. A., Wagner J. A., Mandel G., Goodman R. H. Identification of a cyclic-AMP-responsive element within the rat somatostatin gene. Proc Natl Acad Sci U S A. 1986 Sep;83(18):6682–6686. doi: 10.1073/pnas.83.18.6682. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Morrissey L. C., Barsoum J., Androphy E. J. Trans activation by the bovine papillomavirus E2 protein in Saccharomyces cerevisiae. J Virol. 1989 Oct;63(10):4422–4425. doi: 10.1128/jvi.63.10.4422-4425.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Moskaluk C., Bastia D. DNA bending is induced in an enhancer by the DNA-binding domain of the bovine papillomavirus E2 protein. Proc Natl Acad Sci U S A. 1988 Mar;85(6):1826–1830. doi: 10.1073/pnas.85.6.1826. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Müller-Immerglück M. M., Schaffner W., Matthias P. Transcription factor Oct-2A contains functionally redundant activating domains and works selectively from a promoter but not from a remote enhancer position in non-lymphoid (HeLa) cells. EMBO J. 1990 May;9(5):1625–1634. doi: 10.1002/j.1460-2075.1990.tb08282.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Piña B., Brüggemeier U., Beato M. Nucleosome positioning modulates accessibility of regulatory proteins to the mouse mammary tumor virus promoter. Cell. 1990 Mar 9;60(5):719–731. doi: 10.1016/0092-8674(90)90087-u. [DOI] [PubMed] [Google Scholar]
  40. Ptashne M., Gann A. A. Activators and targets. Nature. 1990 Jul 26;346(6282):329–331. doi: 10.1038/346329a0. [DOI] [PubMed] [Google Scholar]
  41. Richard-Foy H., Hager G. L. Sequence-specific positioning of nucleosomes over the steroid-inducible MMTV promoter. EMBO J. 1987 Aug;6(8):2321–2328. doi: 10.1002/j.1460-2075.1987.tb02507.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Romanczuk H., Thierry F., Howley P. M. Mutational analysis of cis elements involved in E2 modulation of human papillomavirus type 16 P97 and type 18 P105 promoters. J Virol. 1990 Jun;64(6):2849–2859. doi: 10.1128/jvi.64.6.2849-2859.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Sawadogo M., Roeder R. G. Interaction of a gene-specific transcription factor with the adenovirus major late promoter upstream of the TATA box region. Cell. 1985 Nov;43(1):165–175. doi: 10.1016/0092-8674(85)90021-2. [DOI] [PubMed] [Google Scholar]
  44. Schatt M. D., Rusconi S., Schaffner W. A single DNA-binding transcription factor is sufficient for activation from a distant enhancer and/or from a promoter position. EMBO J. 1990 Feb;9(2):481–487. doi: 10.1002/j.1460-2075.1990.tb08134.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Smale S. T., Baltimore D. The "initiator" as a transcription control element. Cell. 1989 Apr 7;57(1):103–113. doi: 10.1016/0092-8674(89)90176-1. [DOI] [PubMed] [Google Scholar]
  46. Smale S. T., Schmidt M. C., Berk A. J., Baltimore D. Transcriptional activation by Sp1 as directed through TATA or initiator: specific requirement for mammalian transcription factor IID. Proc Natl Acad Sci U S A. 1990 Jun;87(12):4509–4513. doi: 10.1073/pnas.87.12.4509. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Sousa R., Dostatni N., Yaniv M. Control of papillomavirus gene expression. Biochim Biophys Acta. 1990 Jun 1;1032(1):19–37. doi: 10.1016/0304-419x(90)90010-x. [DOI] [PubMed] [Google Scholar]
  48. Sowden M., Harrison S., Ashfield R., Kingsman A. J., Kingsman S. M. Multiple cooperative interactions constrain BPV-1 E2 dependent activation of transcription. Nucleic Acids Res. 1989 Apr 25;17(8):2959–2972. doi: 10.1093/nar/17.8.2959. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Spalholz B. A., Byrne J. C., Howley P. M. Evidence for cooperativity between E2 binding sites in E2 trans-regulation of bovine papillomavirus type 1. J Virol. 1988 Sep;62(9):3143–3150. doi: 10.1128/jvi.62.9.3143-3150.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Spalholz B. A., Lambert P. F., Yee C. L., Howley P. M. Bovine papillomavirus transcriptional regulation: localization of the E2-responsive elements of the long control region. J Virol. 1987 Jul;61(7):2128–2137. doi: 10.1128/jvi.61.7.2128-2137.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Spalholz B. A., Yang Y. C., Howley P. M. Transactivation of a bovine papilloma virus transcriptional regulatory element by the E2 gene product. Cell. 1985 Aug;42(1):183–191. doi: 10.1016/s0092-8674(85)80114-8. [DOI] [PubMed] [Google Scholar]
  52. Stanway C. A., Sowden M. P., Wilson L. E., Kingsman A. J., Kingsman S. M. Efficient activation of transcription in yeast by the BPV1 E2 protein. Nucleic Acids Res. 1989 Mar 25;17(6):2187–2196. doi: 10.1093/nar/17.6.2187. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Stringer K. F., Ingles C. J., Greenblatt J. Direct and selective binding of an acidic transcriptional activation domain to the TATA-box factor TFIID. Nature. 1990 Jun 28;345(6278):783–786. doi: 10.1038/345783a0. [DOI] [PubMed] [Google Scholar]
  54. Strähle U., Schmid W., Schütz G. Synergistic action of the glucocorticoid receptor with transcription factors. EMBO J. 1988 Nov;7(11):3389–3395. doi: 10.1002/j.1460-2075.1988.tb03212.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Taylor I. C., Kingston R. E. Factor substitution in a human HSP70 gene promoter: TATA-dependent and TATA-independent interactions. Mol Cell Biol. 1990 Jan;10(1):165–175. doi: 10.1128/mcb.10.1.165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Thierry F., Dostatni N., Arnos F., Yaniv M. Cooperative activation of transcription by bovine papillomavirus type 1 E2 can occur over a large distance. Mol Cell Biol. 1990 Aug;10(8):4431–4437. doi: 10.1128/mcb.10.8.4431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Thierry F., Howley P. M. Functional analysis of E2-mediated repression of the HPV18 P105 promoter. New Biol. 1991 Jan;3(1):90–100. [PubMed] [Google Scholar]
  58. Thierry F., Yaniv M. The BPV1-E2 trans-acting protein can be either an activator or a repressor of the HPV18 regulatory region. EMBO J. 1987 Nov;6(11):3391–3397. doi: 10.1002/j.1460-2075.1987.tb02662.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Ustav M., Stenlund A. Transient replication of BPV-1 requires two viral polypeptides encoded by the E1 and E2 open reading frames. EMBO J. 1991 Feb;10(2):449–457. doi: 10.1002/j.1460-2075.1991.tb07967.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Wefald F. C., Devlin B. H., Williams R. S. Functional heterogeneity of mammalian TATA-box sequences revealed by interaction with a cell-specific enhancer. Nature. 1990 Mar 15;344(6263):260–262. doi: 10.1038/344260a0. [DOI] [PubMed] [Google Scholar]
  61. Wigler M., Silverstein S., Lee L. S., Pellicer A., Cheng Y. c., Axel R. Transfer of purified herpes virus thymidine kinase gene to cultured mouse cells. Cell. 1977 May;11(1):223–232. doi: 10.1016/0092-8674(77)90333-6. [DOI] [PubMed] [Google Scholar]
  62. Wobbe C. R., Struhl K. Yeast and human TATA-binding proteins have nearly identical DNA sequence requirements for transcription in vitro. Mol Cell Biol. 1990 Aug;10(8):3859–3867. doi: 10.1128/mcb.10.8.3859. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Yee C., Krishnan-Hewlett I., Baker C. C., Schlegel R., Howley P. M. Presence and expression of human papillomavirus sequences in human cervical carcinoma cell lines. Am J Pathol. 1985 Jun;119(3):361–366. [PMC free article] [PubMed] [Google Scholar]

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