1887

Abstract

Human papillomavirus type 8 (HPV-8) is one aetiological agent of macular and flat wart-like lesions in patients with epidermodysplasia verruciformis and appears to be closely linked to skin carcinogenesis. A 1.2 kb region of the genome, which was previously shown to contain a viral E2-dependent enhancer, was progressively shortened from both ends with Bal 31. The resulting fragments were tested for their ability to stimulate chloramphenicol acetyltransferase (CAT) expression from the simian virus 40 (SV40) promoter. This analysis showed a complex interaction between cis-active, positive and negative control elements located throughout the non-coding region and the flanking reading frames. Two separate positively acting sequences significantly stimulated expression only in cooperation with a third region, which led to 12-fold, E2-dependent enhancement on its own. A major negative element was not only active in the context of HPV-8 sequences, but also down-regulated SV40 enhancer-promoter-driven CAT expression when cloned downstream of the transcription unit. It acted at the transcriptional level as shown by RNase protection assays and can therefore be regarded as a cis-acting silencer of transcription.

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1990-10-01
2023-02-06
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References

  1. Brand A. H., Breeden L., Abraham J., Sternglanz R., Nasmyth K. 1985; Characterization of a “silencer” in yeast: a DNA sequence with properties opposite to those of a transcriptional enhancer. Cell 41:41–48
    [Google Scholar]
  2. Brand A. H., Micklem G., Nasmyth K. 1987; A yeast silencer contains sequences that can promote autonomous plasmid replication and transcriptional activation. Cell 51:709–719
    [Google Scholar]
  3. Burt D. W., Nakamura N., Kelley P., Dzau V. J. 1989; Identification of negative and positive regulatory elements in the human renin gene. Journal of Biological Chemistry 264:7357–7362
    [Google Scholar]
  4. Cao S. X., Gutman P. D., Dave H. P. G., Schechter A. N. 1989; Identification of a transcriptional silencer in the 5′-flanking region of the human ε-globin gene. Proceedings of the National Academy of Sciences U.S.A.: 865306–5309
    [Google Scholar]
  5. Chin M. T., Hirochika R., Hirochika H., Broker T. R., Chow L. T. 1988; Regulation of human papillomavirus type 11 enhancer and E6 promoter by activating and repressing proteins from the E2 open reading frame: functional and biochemical studies. Journal of Virology 62:2994–3002
    [Google Scholar]
  6. Chin M. T., Broker T. R., Chow L. T. 1989; Identification of a novel constitutive enhancer element and an associated binding protein: implications for human papillomavirus type 11 enhancer regulation. Journal of Virology 63:2967–2976
    [Google Scholar]
  7. Cripe T. P., Haugen T. H., Turk J. P., Tabatabai F., Schmid P. G.III Dürst M., Gissmann L., Roman A., Turek L. P. 1987; 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 Journal 6:3745–3753
    [Google Scholar]
  8. Fuchs P. G., Iftner T., Weninger J., Pfister H. 1986; Epidermodysplasia verruciformis-associated human papillomavirus 8: genomic sequence and comparative analysis. Journal of Virology 58:626–634
    [Google Scholar]
  9. Glri I., Yaniv M. 1988; Structural and mutational analysis of E2 trans-activating proteins of papillomaviruses reveals three distinct functional domains. EMBO Journal 7:2823–2829
    [Google Scholar]
  10. Gissmann L., Pfister H., Zur Hausen H. 1977; Human papilloma viruses (HPV): characterization of four different isolates. Virology 76:569–580
    [Google Scholar]
  11. Gius D., Grossman S., Bedell M. A., Laimins L. A. 1988; Inducible and constitutive enhancer domains in the noncoding region of human papillomavirus type 18. Journal of Virology 62:665–672
    [Google Scholar]
  12. Gloss B., Bernard H. U., Seedorf K., Klock G. 1987; The upstream regulatory region of the human papillomavirus 16 contains an E2 protein-independent enhancer which is specific for cervical carcinoma cells and regulated by glucocorticoid hormones. EMBO Journal 6:3735–3743
    [Google Scholar]
  13. Gorman C. M., Moffat L. F., Howard B. H. 1982; Recombinant genomes which express chloramphenicol acetyltrans- ferase in mammalian cells. Molecular and Cellular Biology 2:1044–1051
    [Google Scholar]
  14. Graham F. L., Van Der Eb A. J. 1973; A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology 52:456–467
    [Google Scholar]
  15. Green M. R., Maniatis T., Melton D. A. 1983; Human β-globin pre-mRNA synthesized in vitro is accurately spliced in Xenopus oocyte nuclei. Cell 32:681–694
    [Google Scholar]
  16. Grindlay G. J., Lanyon W. G., Allan M., Paul J. 1984; Alternative sites of transcription initiation upstream of the canonical cap-site in human gamma-globin and beta-globin genes. Nucleic Acids Research 12:1811–1821
    [Google Scholar]
  17. Hawley-Nelson P., Androphy E. J., Lowy D. R., Schiller J. T. 1988; The specific DNA recognition sequence of the bovine papillomavirus E2 protein is an E2-dependent enhancer. EMBO Journal 7:525–531
    [Google Scholar]
  18. Hirochika H., Broker T. R., Chow L. T. 1987; Enhancers and transacting E2 transcriptional factors of papillomaviruses. Journal of Virology 61:2599–2606
    [Google Scholar]
  19. Hirochika H., Hirochika R., Broker T. R., Chow L. T. 1988; Functional mapping of the human papillomavirus type 11 transcriptional enhancer and its interaction with the trans-acting E2 proteins. Genes and Development 2:54–67
    [Google Scholar]
  20. Iftner T. 1990; Papillomavirus genomes: sequence analysis related to functional aspects. In Papillomaviruses and Human Cancer pp 181–202 Pfister H. Edited by Boca Raton: CRC Press;
    [Google Scholar]
  21. Iftner T., Bierfelder S., Csapo Z., Pfister H. 1988; Involvement of human papillomavirus type 8 genes E6 and E7 in transformation and replication. Journal of Virology 62:3655–3661
    [Google Scholar]
  22. Krubke J., Kraus J., Delius H., Chow L., Broker T., Iftner T., Pfister H. 1987; Genetic relationship among human papillomaviruses associated with benign and malignant tumours of patients with epidermodysplasia verruciformis. Journal of General Virology 68:3091–3103
    [Google Scholar]
  23. Lakshmikumaran M. S., D′Ambrosio E., Laimins L. A., Lin D. T., Furano A. V. 1985; Long interspersed repeated DNA (LINE) causes polymorphism at the rat insulin locus. Molecular and Cellular Biology 5:2197–2203
    [Google Scholar]
  24. Laimins L., Holmgren-König M., Khoury G. 1986; Transcriptional “silencer” element in rat insulin 1 gene locus. Proceedings of the National Academy of Sciences U.S.A.: 833151–3155
    [Google Scholar]
  25. Maniatis T., Fritsch E. F., Sambrook J. 1982 Molecular Cloning: A laboratory Manual New York: Cold Spring Harbor Laboratory;
    [Google Scholar]
  26. Marsh L. J., Erfile M., Wykes E. J. 1984; The pIC-plasmid and phage vectors with versatile cloning sites for recombinant selection by insertion inactivation. Gene 32:481–485
    [Google Scholar]
  27. Maxam A. M., Gilbert W. 1980; Sequencing end-labeled DNA with base-specific chemical cleavages. Methods in Enzymology 65:499–560
    [Google Scholar]
  28. Orth G. 1987; Epidermodysplasia verruciformis. In The Papova- viridae pp 199–244 Salzman N. P., Howley P. M. Edited by New York: Plenum Press;
    [Google Scholar]
  29. Pech M., Rao C. D., Robbins K. C., Aaronson S. A. 1989; Functional identification of regulatory elements within the promoter region of platelet-derived growth factor 2. Molecular and Cellular Biology 9:396–405
    [Google Scholar]
  30. Pfister H. 1988; The papillomaviruses. In Laboratory Diagnosis of Infectious Diseases. Principles and Practice II pp 301–316 Balows A., Hausler W. I.Jr Lennette E. H. Edited by New York: Springer-Verlag;
    [Google Scholar]
  31. Pfister H., Nürnberger F., Gissmann L., Zur Hausen H. 1981; Characterization of a human papillomavirus from epidermodysplasia verruciformis lesions of a patient from Upper-Volta. International Journal of Cancer 27:645–650
    [Google Scholar]
  32. Phelps W. C., Howley P. M. 1987; Transcriptional transactivation by the human papillomavirus type 16 E2 gene product. Journal of Virology 61:1630–1638
    [Google Scholar]
  33. Seeberger R., Haugen T., Turek L., Pfister H. 1987; An enhancer of human papillomavirus type 8 is trans-activated by the bovine papillomavirus type 1 E2 function. Cancer Cells 5:33–38
    [Google Scholar]
  34. Steinberg B. M., Auborn K. J., Brandsma J. L., Taichman L. B. 1987; Tissue site-specific enhancer function of the upstream regulatory region of human papillomavirus type 11 in cultured keratinocytes. Journal of Virology 63:957–960
    [Google Scholar]
  35. Swift F. V., Bhat K., Younghusband H. B., Hamada H. 1987; Characterization of a cell type-specific enhancer found in the human papillomavirus type 18 genome. EMBO Journal 6:1339–1344
    [Google Scholar]
  36. Thierry F., Yaniv M. 1987; The BPV1 E2 trans-acting protein can be either an activator or a repressor of the HPV18 regulatory region. EMBO Journal 6:3391–3397
    [Google Scholar]
  37. Waslyk B., Imler L., Chatton B., Schatz C., Waslyk C. 1988; Negative and positive factors determine the activity of the polyoma virus enhancer a domain in undifferentiated and differentiated cell types. Proceedings of the National Academy of Sciences U.S.A.: 857952–7956
    [Google Scholar]
  38. Westin G., Gerster T., Müller M. M., Schaffner G., Schaffner W. 1987; OVEC, a versatile system to study transcription in mammalian cells and cell-free extracts. Nucleic Acids Research 15:6787–6798
    [Google Scholar]
  39. Wu T., Mounts P. 1988; Transcriptional regulatory elements in the noncoding region of human papillomavirus type 6. Journal of Virology 62:4722–4729
    [Google Scholar]
  40. Zinn K., Dimaio D., Maniatis T. 1983; Identification of two distinct regulatory regions adjacent to the human β-interferon gene. Cell 34:865–879
    [Google Scholar]
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