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. 1990 Feb 11;18(3):465–470. doi: 10.1093/nar/18.3.465

Transcriptional activation of human papillomavirus 16 by nuclear factor I, AP1, steroid receptors and a possibly novel transcription factor, PVF: a model for the composition of genital papillomavirus enhancers.

T Chong 1, W K Chan 1, H U Bernard 1
PMCID: PMC333449  PMID: 2155400

Abstract

Human papillomavirus 16 (HPV-16), which is involved in genital carcinogenesis, contains an enhancer of transcription that is activated by cellular factors rather than by the viral E2 proteins. The activity resides on a 232 bp segment with 5 binding sites for nuclear factor 1 (NF1), 2 for AP1, and 1 for steroid receptors. Deletions and point mutations show that the constitutive enhancer and the steroid response depend on NF1 sites located 5' or 3' of a 65 bp fragment with AP1 sites that by itself shows little activity. Enhancement through a fragment with AP1 and NF1 sites is strongly reduced by mutation of the AP1 sites, or by mutation of the sequence AGGCACATAT. Sequence comparison and footprint analysis make it likely that this sequence binds a novel transcription factor which we call PVF. Fragments with one or several binding sites only for NF1, or AP1, or PVF exhibit little enhancement by themselves, suggesting the functional dependence of the HPV-16 enhancer on the cooperation of these factors. A comparison of our findings with the genomes and transcription factor binding sites of HPV-6, 11, 18, 31 and 33 lead us to propose a model of the composition of enhancers of genital papillomaviruses.

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Selected References

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

  1. Angel P., Imagawa M., Chiu R., Stein B., Imbra R. J., Rahmsdorf H. J., Jonat C., Herrlich P., Karin M. Phorbol ester-inducible genes contain a common cis element recognized by a TPA-modulated trans-acting factor. Cell. 1987 Jun 19;49(6):729–739. doi: 10.1016/0092-8674(87)90611-8. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Chan W. K., Klock G., Bernard H. U. Progesterone and glucocorticoid response elements occur in the long control regions of several human papillomaviruses involved in anogenital neoplasia. J Virol. 1989 Aug;63(8):3261–3269. doi: 10.1128/jvi.63.8.3261-3269.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chin M. T., Broker T. R., Chow L. T. Identification of a novel constitutive enhancer element and an associated binding protein: implications for human papillomavirus type 11 enhancer regulation. J Virol. 1989 Jul;63(7):2967–2976. doi: 10.1128/jvi.63.7.2967-2976.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cole S. T., Danos O. Nucleotide sequence and comparative analysis of the human papillomavirus type 18 genome. Phylogeny of papillomaviruses and repeated structure of the E6 and E7 gene products. J Mol Biol. 1987 Feb 20;193(4):599–608. doi: 10.1016/0022-2836(87)90343-3. [DOI] [PubMed] [Google Scholar]
  6. Cole S. T., Streeck R. E. Genome organization and nucleotide sequence of human papillomavirus type 33, which is associated with cervical cancer. J Virol. 1986 Jun;58(3):991–995. doi: 10.1128/jvi.58.3.991-995.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cripe T. P., Haugen T. H., Turk J. P., Tabatabai F., Schmid P. G., 3rd, Dürst M., Gissmann L., Roman A., Turek L. P. Transcriptional regulation of the human papillomavirus-16 E6-E7 promoter by a keratinocyte-dependent enhancer, and by viral E2 trans-activator and repressor gene products: implications for cervical carcinogenesis. EMBO J. 1987 Dec 1;6(12):3745–3753. doi: 10.1002/j.1460-2075.1987.tb02709.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dartmann K., Schwarz E., Gissmann L., zur Hausen H. The nucleotide sequence and genome organization of human papilloma virus type 11. Virology. 1986 May;151(1):124–130. doi: 10.1016/0042-6822(86)90110-8. [DOI] [PubMed] [Google Scholar]
  9. Gloss B., Bernard H. U., Seedorf K., Klock G. The upstream regulatory region of the human papilloma virus-16 contains an E2 protein-independent enhancer which is specific for cervical carcinoma cells and regulated by glucocorticoid hormones. EMBO J. 1987 Dec 1;6(12):3735–3743. doi: 10.1002/j.1460-2075.1987.tb02708.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gloss B., Chong T., Bernard H. U. Numerous nuclear proteins bind the long control region of human papillomavirus type 16: a subset of 6 of 23 DNase I-protected segments coincides with the location of the cell-type-specific enhancer. J Virol. 1989 Mar;63(3):1142–1152. doi: 10.1128/jvi.63.3.1142-1152.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gloss B., Yeo-Gloss M., Meisterenst M., Rogge L., Winnacker E. L., Bernard H. U. Clusters of nuclear factor I binding sites identify enhancers of several papillomaviruses but alone are not sufficient for enhancer function. Nucleic Acids Res. 1989 May 11;17(9):3519–3533. doi: 10.1093/nar/17.9.3519. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Goldsborough M. D., DiSilvestre D., Temple G. F., Lorincz A. T. Nucleotide sequence of human papillomavirus type 31: a cervical neoplasia-associated virus. Virology. 1989 Jul;171(1):306–311. doi: 10.1016/0042-6822(89)90545-x. [DOI] [PubMed] [Google Scholar]
  13. Hirochika H., Hirochika R., Broker T. R., Chow L. T. Functional mapping of the human papillomavirus type 11 transcriptional enhancer and its interaction with the trans-acting E2 proteins. Genes Dev. 1988 Jan;2(1):54–67. doi: 10.1101/gad.2.1.54. [DOI] [PubMed] [Google Scholar]
  14. Lambert P. F., Baker C. C., Howley P. M. The genetics of bovine papillomavirus type 1. Annu Rev Genet. 1988;22:235–258. doi: 10.1146/annurev.ge.22.120188.001315. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Mermod N., O'Neill E. A., Kelly T. J., Tjian R. The proline-rich transcriptional activator of CTF/NF-I is distinct from the replication and DNA binding domain. Cell. 1989 Aug 25;58(4):741–753. doi: 10.1016/0092-8674(89)90108-6. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. Schwarz E., Dürst M., Demankowski C., Lattermann O., Zech R., Wolfsperger E., Suhai S., zur Hausen H. DNA sequence and genome organization of genital human papillomavirus type 6b. EMBO J. 1983;2(12):2341–2348. doi: 10.1002/j.1460-2075.1983.tb01744.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. Smotkin D., Wettstein F. O. Transcription of human papillomavirus type 16 early genes in a cervical cancer and a cancer-derived cell line and identification of the E7 protein. Proc Natl Acad Sci U S A. 1986 Jul;83(13):4680–4684. doi: 10.1073/pnas.83.13.4680. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Swift F. V., Bhat K., Younghusband H. B., Hamada H. Characterization of a cell type-specific enhancer found in the human papilloma virus type 18 genome. EMBO J. 1987 May;6(5):1339–1344. doi: 10.1002/j.1460-2075.1987.tb02373.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Vogt P. K., Bos T. J. The oncogene jun and nuclear signalling. Trends Biochem Sci. 1989 May;14(5):172–175. doi: 10.1016/0968-0004(89)90268-5. [DOI] [PubMed] [Google Scholar]
  23. Wingender E. Compilation of transcription regulating proteins. Nucleic Acids Res. 1988 Mar 25;16(5):1879–1902. doi: 10.1093/nar/16.5.1879. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Wu T. C., Mounts P. Transcriptional regulatory elements in the noncoding region of human papillomavirus type 6. J Virol. 1988 Dec;62(12):4722–4729. doi: 10.1128/jvi.62.12.4722-4729.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]

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