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. 1993 Sep;67(9):5668–5676. doi: 10.1128/jvi.67.9.5668-5676.1993

Cooperative DNA binding of the bovine papillomavirus E2 transcriptional activator is antagonized by truncated E2 polypeptides.

P Monini 1, I L Blitz 1, E Cassai 1
PMCID: PMC237974  PMID: 8394466

Abstract

Cooperative DNA binding of the bovine papillomavirus type 1 (BPV-1) E2 transcriptional activator (E2-TA) is thought to play a role in the transcriptional synergism of multiple E2-responsive DNA elements (J. Ham, N. Dostatni, J.-M. Gauthier, and M. Yaniv, Trends Biochem. Sci. 16:440-444, 1991). Binding-equilibrium considerations show that such involvement is unlikely, thereby suggesting that the E2-TA cooperative capacity may have evolved to play other, different roles. The role of cooperative interactions in the antagonistic activity of BPV-1-positive and BPV-1-negative E2 regulatory proteins was investigated by an in vitro quantitative gel shift assay. Viral repressor E2-TR, a truncated peptide encompassing the activator DNA-binding domain, possesses a small but measurable cooperative capacity. Furthermore, the minimal E2 DNA-binding domain interacts with the activator in a positive, heterocooperative manner. As a result, the in vitro competition of full-length and truncated E2 peptides appears to be (macroscopically) noncooperative. This heterocooperative effect is probably dominant in latently infected G0-G1 cells, in which repressor E2-TR is 10- to 20-fold more abundant than the activator. The data are discussed considering the possible role of homo- and heterocooperative DNA binding in E2-conditional gene expression.

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Selected References

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

  1. Ackers G. K., Shea M. A., Smith F. R. Free energy coupling within macromolecules. The chemical work of ligand binding at the individual sites in co-operative systems. J Mol Biol. 1983 Oct 15;170(1):223–242. doi: 10.1016/s0022-2836(83)80234-4. [DOI] [PubMed] [Google Scholar]
  2. Androphy E. J., Lowy D. R., Schiller J. T. Bovine papillomavirus E2 trans-activating gene product binds to specific sites in papillomavirus DNA. Nature. 1987 Jan 1;325(6099):70–73. doi: 10.1038/325070a0. [DOI] [PubMed] [Google Scholar]
  3. Auron P. E., Sullivan D., Fenton M. J., Clark B. D., Cole E. S., Galson D. L., Peters L., Teller D. The Nucleic Acid Blot Analyzer II. ANALYZE, an image analysis software package for molecular biology. Biotechniques. 1988 Apr;6(4):347–353. [PubMed] [Google Scholar]
  4. Baniahmad C., Muller M., Altschmied J., Renkawitz R. Co-operative binding of the glucocorticoid receptor DNA binding domain is one of at least two mechanisms for synergism. J Mol Biol. 1991 Nov 20;222(2):155–165. doi: 10.1016/0022-2836(91)90202-h. [DOI] [PubMed] [Google Scholar]
  5. Barsoum J., Prakash S. S., Han P., Androphy E. J. Mechanism of action of the papillomavirus E2 repressor: repression in the absence of DNA binding. J Virol. 1992 Jun;66(6):3941–3945. doi: 10.1128/jvi.66.6.3941-3945.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bedrosian C. L., Bastia D. The DNA-binding domain of HPV-16 E2 protein interaction with the viral enhancer: protein-induced DNA bending and role of the nonconserved core sequence in binding site affinity. Virology. 1990 Feb;174(2):557–575. doi: 10.1016/0042-6822(90)90109-5. [DOI] [PubMed] [Google Scholar]
  7. Burnett S., Ström A. C., Jareborg N., Alderborn A., Dillner J., Moreno-Lopez J., Pettersson U., Kiessling U. Induction of bovine papillomavirus E2 gene expression and early region transcription by cell growth arrest: correlation with viral DNA amplification and evidence for differential promoter induction. J Virol. 1990 Nov;64(11):5529–5541. doi: 10.1128/jvi.64.11.5529-5541.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Carey M., Lin Y. S., Green M. R., Ptashne M. A mechanism for synergistic activation of a mammalian gene by GAL4 derivatives. Nature. 1990 May 24;345(6273):361–364. doi: 10.1038/345361a0. [DOI] [PubMed] [Google Scholar]
  9. Choe J., Vaillancourt P., Stenlund A., Botchan M. Bovine papillomavirus type 1 encodes two forms of a transcriptional repressor: structural and functional analysis of new viral cDNAs. J Virol. 1989 Apr;63(4):1743–1755. doi: 10.1128/jvi.63.4.1743-1755.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Cordingley M. G., Hager G. L. Binding of multiple factors to the MMTV promoter in crude and fractionated nuclear extracts. Nucleic Acids Res. 1988 Jan 25;16(2):609–628. doi: 10.1093/nar/16.2.609. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. 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]
  13. 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]
  14. Giniger E., Ptashne M. Cooperative DNA binding of the yeast transcriptional activator GAL4. Proc Natl Acad Sci U S A. 1988 Jan;85(2):382–386. doi: 10.1073/pnas.85.2.382. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. Gius D., Grossman S., Bedell M. A., Laimins L. A. Inducible and constitutive enhancer domains in the noncoding region of human papillomavirus type 18. J Virol. 1988 Mar;62(3):665–672. doi: 10.1128/jvi.62.3.665-672.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Gross D. S., Garrard W. T. Nuclease hypersensitive sites in chromatin. Annu Rev Biochem. 1988;57:159–197. doi: 10.1146/annurev.bi.57.070188.001111. [DOI] [PubMed] [Google Scholar]
  18. Ham J., Dostatni N., Arnos F., Yaniv M. Several different upstream promoter elements can potentiate transactivation by the BPV-1 E2 protein. EMBO J. 1991 Oct;10(10):2931–2940. doi: 10.1002/j.1460-2075.1991.tb07843.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Ham J., Dostatni N., Gauthier J. M., Yaniv M. The papillomavirus E2 protein: a factor with many talents. Trends Biochem Sci. 1991 Nov;16(11):440–444. doi: 10.1016/0968-0004(91)90172-r. [DOI] [PubMed] [Google Scholar]
  20. Hubbert N. L., Schiller J. T., Lowy D. R., Androphy E. J. Bovine papilloma virus-transformed cells contain multiple E2 proteins. Proc Natl Acad Sci U S A. 1988 Aug;85(16):5864–5868. doi: 10.1073/pnas.85.16.5864. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Jencks W. P. On the attribution and additivity of binding energies. Proc Natl Acad Sci U S A. 1981 Jul;78(7):4046–4050. doi: 10.1073/pnas.78.7.4046. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kakidani H., Ptashne M. GAL4 activates gene expression in mammalian cells. Cell. 1988 Jan 29;52(2):161–167. doi: 10.1016/0092-8674(88)90504-1. [DOI] [PubMed] [Google Scholar]
  23. Knight J. D., Li R., Botchan M. The activation domain of the bovine papillomavirus E2 protein mediates association of DNA-bound dimers to form DNA loops. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3204–3208. doi: 10.1073/pnas.88.8.3204. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Laimins L. A., Khoury G., Gorman C., Howard B., Gruss P. Host-specific activation of transcription by tandem repeats from simian virus 40 and Moloney murine sarcoma virus. Proc Natl Acad Sci U S A. 1982 Nov;79(21):6453–6457. doi: 10.1073/pnas.79.21.6453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. 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]
  26. Lambert P. F., Monk B. C., Howley P. M. Phenotypic analysis of bovine papillomavirus type 1 E2 repressor mutants. J Virol. 1990 Feb;64(2):950–956. doi: 10.1128/jvi.64.2.950-956.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Lambert P. F., Spalholz B. A., Howley P. M. A transcriptional repressor encoded by BPV-1 shares a common carboxy-terminal domain with the E2 transactivator. Cell. 1987 Jul 3;50(1):69–78. doi: 10.1016/0092-8674(87)90663-5. [DOI] [PubMed] [Google Scholar]
  28. LeBowitz J. H., Clerc R. G., Brenowitz M., Sharp P. A. The Oct-2 protein binds cooperatively to adjacent octamer sites. Genes Dev. 1989 Oct;3(10):1625–1638. doi: 10.1101/gad.3.10.1625. [DOI] [PubMed] [Google Scholar]
  29. 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]
  30. 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]
  31. Lin S. Y., Riggs A. D. Lac repressor binding to non-operator DNA: detailed studies and a comparison of eequilibrium and rate competition methods. J Mol Biol. 1972 Dec 30;72(3):671–690. doi: 10.1016/0022-2836(72)90184-2. [DOI] [PubMed] [Google Scholar]
  32. Lin Y. S., Carey M. F., Ptashne M., Green M. R. GAL4 derivatives function alone and synergistically with mammalian activators in vitro. Cell. 1988 Aug 26;54(5):659–664. doi: 10.1016/s0092-8674(88)80010-2. [DOI] [PubMed] [Google Scholar]
  33. Lin Y. S., Carey M., Ptashne M., Green M. R. How different eukaryotic transcriptional activators can cooperate promiscuously. Nature. 1990 May 24;345(6273):359–361. doi: 10.1038/345359a0. [DOI] [PubMed] [Google Scholar]
  34. Martinez E., Wahli W. Cooperative binding of estrogen receptor to imperfect estrogen-responsive DNA elements correlates with their synergistic hormone-dependent enhancer activity. EMBO J. 1989 Dec 1;8(12):3781–3791. doi: 10.1002/j.1460-2075.1989.tb08555.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. 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]
  36. McGhee J. D., von Hippel P. H. Theoretical aspects of DNA-protein interactions: co-operative and non-co-operative binding of large ligands to a one-dimensional homogeneous lattice. J Mol Biol. 1974 Jun 25;86(2):469–489. doi: 10.1016/0022-2836(74)90031-x. [DOI] [PubMed] [Google Scholar]
  37. 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]
  38. 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]
  39. Moskaluk C. A., Bastia D. Interaction of the bovine papillomavirus type 1 E2 transcriptional control protein with the viral enhancer: purification of the DNA-binding domain and analysis of its contact points with DNA. J Virol. 1988 Jun;62(6):1925–1931. doi: 10.1128/jvi.62.6.1925-1931.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. 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]
  41. Murphy S., Yoon J. B., Gerster T., Roeder R. G. Oct-1 and Oct-2 potentiate functional interactions of a transcription factor with the proximal sequence element of small nuclear RNA genes. Mol Cell Biol. 1992 Jul;12(7):3247–3261. doi: 10.1128/mcb.12.7.3247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Poellinger L., Roeder R. G. Octamer transcription factors 1 and 2 each bind to two different functional elements in the immunoglobulin heavy-chain promoter. Mol Cell Biol. 1989 Feb;9(2):747–756. doi: 10.1128/mcb.9.2.747. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Ponglikitmongkol M., White J. H., Chambon P. Synergistic activation of transcription by the human estrogen receptor bound to tandem responsive elements. EMBO J. 1990 Jul;9(7):2221–2231. doi: 10.1002/j.1460-2075.1990.tb07392.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Prakash S. S., Grossman S. R., Pepinsky R. B., Laimins L. A., Androphy E. J. Amino acids necessary for DNA contact and dimerization imply novel motifs in the papillomavirus E2 trans-activator. Genes Dev. 1992 Jan;6(1):105–116. doi: 10.1101/gad.6.1.105. [DOI] [PubMed] [Google Scholar]
  45. Ptashne M. How eukaryotic transcriptional activators work. Nature. 1988 Oct 20;335(6192):683–689. doi: 10.1038/335683a0. [DOI] [PubMed] [Google Scholar]
  46. Schüle R., Muller M., Kaltschmidt C., Renkawitz R. Many transcription factors interact synergistically with steroid receptors. Science. 1988 Dec 9;242(4884):1418–1420. doi: 10.1126/science.3201230. [DOI] [PubMed] [Google Scholar]
  47. Schüle R., Muller M., Otsuka-Murakami H., Renkawitz R. Cooperativity of the glucocorticoid receptor and the CACCC-box binding factor. Nature. 1988 Mar 3;332(6159):87–90. doi: 10.1038/332087a0. [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. 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]
  53. 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]
  54. Tsai S. Y., Tsai M. J., O'Malley B. W. Cooperative binding of steroid hormone receptors contributes to transcriptional synergism at target enhancer elements. Cell. 1989 May 5;57(3):443–448. doi: 10.1016/0092-8674(89)90919-7. [DOI] [PubMed] [Google Scholar]
  55. Yang L., Mohr I., Li R., Nottoli T., Sun S., Botchan M. Transcription factor E2 regulates BPV-1 DNA replication in vitro by direct protein-protein interaction. Cold Spring Harb Symp Quant Biol. 1991;56:335–346. doi: 10.1101/sqb.1991.056.01.040. [DOI] [PubMed] [Google Scholar]
  56. Zaret K. S., Yamamoto K. R. Reversible and persistent changes in chromatin structure accompany activation of a glucocorticoid-dependent enhancer element. Cell. 1984 Aug;38(1):29–38. doi: 10.1016/0092-8674(84)90523-3. [DOI] [PubMed] [Google Scholar]

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