1887

Abstract

Human papillomavirus type 8 (HPV-8) is a strictly cutaneous oncogenic virus known to induce malignant skin lesions in patients. Our study shows that sequences surrounding transcription start sites of the HPV-8 oncogene E6 (nt 175–179) and comprising the presumable CCAAC and TATA boxes of the E6 promoter P contain a cluster of four motifs similar to the DNA recognition site of the multifunctional cellular transcription factor 1 (YY1). Using DNase I footprinting and gel retardation tests it could be demonstrated that three of these motifs indeed act as YY1 binding sites. To test their functional relevance for P activity, engineered YY1 binding site mutants were analysed in the context of a P test vector using transient expression assays with human keratinocytes. YY1 turned out to exert both positive and negative effects upon the activity of the HPV-8 E6 promoter; binding of YY1 to a site upstream of the promoter’s cap-position (BS1) activated transcription, whereas the downstream site (BS2) mediated repression. The second downstream YY1 binding site (BS3) seemed to play an auxiliary role, enhancing the negative effect of YY1 BS2. These observations define YY1 as an important cellular protein involved in the control of E6 oncogene expression of the skin-specific ‘high risk’ HPV-8 and emphasize the potential regulatory role of sequences located downstream of the transcription start site.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-78-12-3287
1997-12-01
2024-12-07
Loading full text...

Full text loading...

/deliver/fulltext/jgv/78/12/9400979.html?itemId=/content/journal/jgv/10.1099/0022-1317-78-12-3287&mimeType=html&fmt=ahah

References

  1. Ausubel F. M., Brent R., Kingston R. E., Moore D. D., Seidman J. G., Smith J. A., Struhl K.editor 1995 Current Protocols in Molecular Biology New York: John Wiley & Sons;
    [Google Scholar]
  2. Bauknecht T., Angel P., Royer H.-D., zur Hausen H. 1992; Identification of a negative regulatory domain in the human papillomavirus type 18 promoter: interaction with the transcriptional repressor YY1. EMBO Journal 11:4607–4617
    [Google Scholar]
  3. Bauknecht T., Jundt F., Herr I., Oehler T., Delius H., Shi Y., Angel P., zur Hausen H. 1995; A switch region determines the cell type-specific positive or negative action of YY1 on the activity of the human papillomavirus type 18 promoter. Journal of Virology 69:1–12
    [Google Scholar]
  4. Bauknecht T., See R. H., Shi Y. 1996; A novel C/EBP β-YY1 complex controls the cell-type-specific activity of the human papillomavirus type 18 upstream regulatory region. Journal of Virology 70:7695–7705
    [Google Scholar]
  5. Böhm S., Wilczynski S. P., Pfister H., Iftner T. 1993; The predominant mRNA class in HPV16-infected anogenital neoplasia does not encode the E6 or the E7 protein. International Journal of Cancer 55:791–798
    [Google Scholar]
  6. Boshart M., Kluppel M., Schmidt A., Luckow B. 1992; Reporter constructs with low background activity utilizing the CAT gene. Gene 110:129–130
    [Google Scholar]
  7. Chen S., Mills L., Perry P., Riddle S., Wobig R., Lown R., Millette R. I. 1992; Transactivation of the major capsid protein of herpes simplex virus type 1 requires a cellular transcription factor. Journal of Virology 66:4304–4314
    [Google Scholar]
  8. Chomczynski P., Sacchi N. 1987; Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Analytical Biochemistry 162:156–158
    [Google Scholar]
  9. Dong X.-P., Stubenrauch F., Beyer-Finkler E., Pfister H. 1994; Prevalence of deletions of YYl-binding sites in episomal HPV 16 DNA from cervical cancers. International Journal of Cancer 58:803–808
    [Google Scholar]
  10. Dürst M., Glitz D., Schneider A., zur Hausen H. 1992; Human papillomavirus type 16 (HPV16) gene expression and DNA replication in cervical neoplasia: analysis by in situ hybridization. Virology 189:132–140
    [Google Scholar]
  11. Ensser A., Pfister H. 1990; Epidermodysplasia verruciformis associated human papillomaviruses present a subgenus-specific organization of the regulatory genome region. Nucleic Acids Research 18:3919–3922
    [Google Scholar]
  12. Flanagan J. R., Becker K. G., Ennist D. L., Gleason S. L., Driggers P. H., Levi B.-Z., Appella E., Ozato K. 1992; Cloning of a negative transcription factor that binds to the upstream conserved region of Moloney murine leukemia virus. Molecular and Cellular Biology 12:38–44
    [Google Scholar]
  13. Fuchs P. G., Pfister H. 1996; Papillomaviruses in epidermodysplasia verruciformis. In Papillomavirus Reviews pp. 253–261 Lacey C. Edited by Leeds: Leeds University Press;
    [Google Scholar]
  14. Fuchs P. G., Pfister H. 1997; Molecular biology of HPV and mechanisms of keratinocyte transformation. In Human Papillomavirus Infections in Dermatovenerology pp. 15–46 Gross G., Von Krogh G. Edited by Boca Raton, Fla: CRC Press;
    [Google Scholar]
  15. 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]
  16. Haller K., Stubenrauch F., Pfister H. 1995; Differentiation-dependent transcription of the epidermodysplasia verruciformis-associated human papillomavirus type 5 in benign lesions. Virology 214:245–255
    [Google Scholar]
  17. Higgins G. D., Uzelin D. M., Phillips G. E., McEvoy P., Marin R., Burrell C. J. 1992; Transcription patterns of human papillomavirus type 16 in genital intraepithelial neoplasia : evidence for promoter usage within the E7 open reading frame during epithelial differentiation. Journal of General Virology 73:2047–2057
    [Google Scholar]
  18. Horn S., Pfister H., Fuchs P. G. 1993; Constitutive transcriptional activator of epidermodysplasia verruciformis-associated human papil-lomavirus 8. Virology 196:674–681
    [Google Scholar]
  19. Hyde-DeRuyscher R. P., Jennings E., Shenk T. 1995; DNA binding sites for the transcriptional activator/repressor YY1. Nucleic Acids Research 23:4457–4465
    [Google Scholar]
  20. 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]
  21. Iftner T., Sagner G., Pfister H., Wettstein F. O. 1990; The E7 protein of human papillomavirus 8 is a nonphosphorylated protein of 17 kDa and can be generated by two different mechanisms. Virology 179:428–436
    [Google Scholar]
  22. Jablonska S., Dabrowski J., Jakubowicz K. 1972; Epidermodysplasia verruciformis as a model in studies on the role of papovaviruses in oncogenesis. Cancer Research 32:583–589
    [Google Scholar]
  23. Jundt F., Herr I., Angel P., zur Hausen H., Bauknecht T. 1995; Transcriptional control of human papillomavirus type 18 oncogene expression in different cell lines : role of transcription factor YY1. Virus Genes 11:53–58
    [Google Scholar]
  24. Kiyono T., Nashima K., Ishibashi M. 1989; The primary structure of major viral RNA in a rat cell line transformed with type 47 human papillomavirus DNA and the transforming activity of its cDNA and E6 gene. Virology 173:551–565
    [Google Scholar]
  25. Kiyono T., Hiraiwa A., Ishibashi M. 1992; Differences in transforming activity and coded amino acid sequence among E6 genes of several papillomaviruses associated with epidermodysplasia verruciformis. Virology 186:628–639
    [Google Scholar]
  26. Kozak M. 1984; Compilat ion and analysis of sequences upstream from the translational start site in eukaryotic mRNAs. Nucleic Acids Research 12:857–872
    [Google Scholar]
  27. 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]
  28. Lee T.-C., Shi Y., Schwartz R. J. 1992; Displacement of BrdUrd-induced YY1 by serum response factor activates skeletal α-actin transcription in embryonic myoblasts. Proceedings of the National Academy of Sciences, USA 89:9814–9818
    [Google Scholar]
  29. Liu R., Baillie J., Sissons J. G. P., Sinclair J. H. 1994; The transcription factor YY1 binds to negative regulatory elements in the human cytomegalovirus major immediate early enhancer/promoter and mediates repression in non-permissive cells. Nucleic Acids Research 22:2453–2459
    [Google Scholar]
  30. Margolis D. M., Somasundaran M., Green M. R. 1994; Human transcription factor YY1 represses human immunodeficiency virus type 1 transcription and virion production. Journal of Virology 68:905–910
    [Google Scholar]
  31. Martelli F., Iacobini C., Caruso M., Felsani A. 1996; Characterization of two novel YY1 binding sites in the polyomavirus late promoter. Journal of Virology 70:1433–1438
    [Google Scholar]
  32. May M., Dong X.-P., Beyer-Finkler E., Stubenrauch F., Fuchs P. G., Pfister H. 1994a; The E6/E7 promoter of extrachromosomal HPV16 DNA in cervical cancers escapes from cellular repression by mutation of target sequences for YY1. EMBO Journal 13:1460–1466
    [Google Scholar]
  33. May M., Grassmann K., Pfister H., Fuchs P. G. 1994b; Transcriptional silencer of the human papillomavirus type 8 late promoter interacts alternatively with the viral trans activator E2 or with a cellular factor. Journal of Virology 68:3612–3619
    [Google Scholar]
  34. Momoeda M., Kawase M., Jane S. M., Miyamura K., Young N. S., Kajigaya S. 1994; The transcriptional regulator YY1 binds to the 5′-terminal region of B19 parvovirus and regulates P6 promoter activity. Journal of Virology 68:7159–7168
    [Google Scholar]
  35. Montalvo E. A., Cottam M., Hill S., Wang Y.-C. J. 1995; YY1 binds to and regulates cis-acting negative elements in the Epstein-Barr virus BZLF promoter. Journal of Virology 69:4158–4165
    [Google Scholar]
  36. O’Connor M. J., Tan S.-H., Tan C.-H., Bernard H.-U. 1996; YY1 represses human papillomavirus type 16 transcription by quenching AP-1 activity. Journal of Virology 70:6529–6539
    [Google Scholar]
  37. Orth G. 1987; Epidermodysplasia verruciformis. In The Papovaviridae 2 pp. 199–234 Salzman H. P., Howley P. M. Edited by New York: Plenum Press;
    [Google Scholar]
  38. Purdie K. J., Sexton C. J., Proby C. M., Glover M. T., Williams A. T., Stables K. J., Leigh I. M. 1993; Malignant transformation of cutaneous lesions in renal allograft patients : a role for human papillomavirus. Cancer Research 53:5328–5333
    [Google Scholar]
  39. Reh H., Pfister H. 1990; Human papillomavirus type 8 contains cis-active positive and negative transcriptional control sequences. Journal of General Virology 71:2457–2462
    [Google Scholar]
  40. Satyamoorthy K., Park K., Atchison M. L., Howe C. C. 1993; The intracisternal A-particle upstream element interacts with transcription factor YY1 to activate transcription: pleiotropic effects of YY1 on distinct DNA promoter elements. Molecular and Cellular Biology 13:6621–6628
    [Google Scholar]
  41. Seto E., Shi Y., Shenk T. 1991; YY1 is an initiator sequencebinding protein that directs and activates transcription in vitro. Nature 354:241–245
    [Google Scholar]
  42. Shah K. V., Howley P. M. 1996; Papillomaviruses. In Fields Virology, 3rd edn. pp. 2077–2109 Fields B. N., Knipe D. M., Howley P. M. Edited by Philadelphia: Lippincott-Raven;
    [Google Scholar]
  43. Shi Y., Seto E., Chang L.-S., Shenk T. 1991; Transcriptional repression by YY1, a human GLI-Krüppel-related protein, and relief of repression by adenovirus E1A protein. Cell 67:377–388
    [Google Scholar]
  44. Shrivastava A., Calame K. 1994; An analysis ofgenes regulated by the multi-functional transcriptional regulator Yin Yang-1. Nucleic Acids Research 22:5151–5155
    [Google Scholar]
  45. Steger G., Corbach S. 1997; Dose-dependent regulation of the promoter of human papillomavirus type 18 by the viral E2 protein. Journal of Virology 71:50–58
    [Google Scholar]
  46. Stoler M. H., Rhodes C. R., Whitbeck A., Wolinsky S. M., Chow L. T., Broker T. R. 1992; Human papillomavirus type 16 and 18 gene expression in cervical neoplasias. Human Pathology 23:117–128
    [Google Scholar]
  47. Stubenrauch F., Malejczyk J., Fuchs P. G., Pfister H. 1992; Late promoter of human papillomavirus type 8 and its regulation. Journal of Virology 66:3485–3493
    [Google Scholar]
  48. Stubenrauch F., Leigh I. M., Pfister H. 1996; E2 represses the late gene promoter of human papillomavirus type 8 at high concentrations by interfering with cellular factors. Journal of Virology 70:119–126
    [Google Scholar]
  49. Wandersee N. J., Ferris R. C., Ginder G. D. 1996; Intronic and flanking sequences are required to silence enhancement of an embryonic beta-type globin gene. Molecular and Cellular Biology 16:236–246
    [Google Scholar]
  50. Zock C., Iselt A., Doerfler W. 1993; A unique mitigator sequence determines the species specificity of the major late promoter in adenovirus type 12 DNA. Journal of Virology 67:682–693
    [Google Scholar]
  51. zur Hausen H. 1994; Molecular pathogenesis of cancer of the cervix and its causation by specific human papillomavirus types. Current Topics in Microbiology and Immunology 186:131–156
    [Google Scholar]
/content/journal/jgv/10.1099/0022-1317-78-12-3287
Loading
/content/journal/jgv/10.1099/0022-1317-78-12-3287
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error