1887

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Volume 73, Issue 1

Repression of the hepatitis B virus enhancer by a cellular factor Free

Abstract

The enhancer element of hepatitis B virus (HBV) regulates the transcription of all HBV mRNA, including the pregenomic mRNA used during replication. This pregenomic mRNA is transcribed from the core gene promoter which is located 500 bp downstream from the HBV enhancer element. To examine the effect of the HBV enhancer on the activity of the core gene promoter, we constructed various plasmids containing different combinations of HBV enhancer and core gene promoter sequences regulating the expression of the chloramphenicol acetyltransferase gene. When the HBV enhancer was positioned immediately adjacent to the core gene promoter, the enhancer increased the activity of the core gene promoter nearly 30-fold. In contrast, the HBV enhancer only modestly stimulated the core gene promoter (less than threefold) at its native position in the HBV genome. This weak HBV enhancer activity was due to a DNA sequence located between the enhancer and the core gene promoter and not due to the increased distance between the enhancer and the core gene promoter. Competition experiments demonstrated that a trans-acting factor(s) bound this sequence and repressed the enhancer. This DNA sequence contains the C/EBP, AP-1 and NF-1 regulatory sites. No inhibition of enhancer activity was observed when only the AP-1 and C/EBP sites were present. Repression of the HBV enhancer was not detected when the NF-1 site was disrupted, indicating that the NF-1 site was involved in the suppression of the HBV enhancer.

  • Received:
  • Accepted:
  • Published Online:
© Journal of General Virology 1992
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1992-01-01
2024-04-23
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References

  1. Antonucci T. K., Rutter W. J. 1989; Hepatitis B virus promoters are regulated by the HBV enhancer in a tissue-specific manner. Journal of Virology 63:579–583
     [Google Scholar]
  2. Bartenschlager R., Schaller H. 1988; The amino-terminal domain of the hepadnaviral P-gene encodes the terminal protein (genome-linked protein) believed to prime reverse transcription. EMBO Journal 7:4185–4192
     [Google Scholar]
  3. Bavand M. R., Laub O. 1988; Two proteins with reverse transcriptase activities associated with hepatitis B virus-like particles. Journal of Virology 62:626–628
     [Google Scholar]
  4. Ben-Levy R., Faktor O., Berger I., Shaul Y. 1989; Cellular factors that interact with the hepatitis B virus enhancer. Molecular and Cellular Biology 9:1804–1809
     [Google Scholar]
  5. Bulla G., Siddiqui A. 1988; The hepatitis B virus enhancer modulates transcription of the hepatitis B virus surface antigen gene from an internal location. Journal of Virology 62:1437–1441
     [Google Scholar]
  6. Caselmann W. H., Meyer M., Kekule A. S., Lauer U., Hofschneider P. H., Koshy R. 1990; A trans-activator function is generated by integration of hepatitis B virus preS/S sequences in human hepatocellular carcinoma DNA. Proceedings of the National Academy of Sciences, U.S.A 87:2970–2974
     [Google Scholar]
  7. Cummings I. W., Browne J. K., Salser W. A., Tyler G. V., Snyder R. L., Smolec J. M., Summers J. 1980; Isolation, characterization, and comparison of recombinant DNAs derived from genomes of human hepatitis B virus and woodchuck hepatitis virus. Proceedings of the National Academy of Sciences, U.S.A 77:1842–1846
     [Google Scholar]
  8. Faktor O., Budlovsky S., Ben-Levy R., Shaul Y. 1990; A single element within the hepatitis B virus enhancer binds multiple proteins and responds to multiple stimuli. Journal of Virology 64:1861–1863
     [Google Scholar]
  9. Ganem D., Varmus H. E. 1987; The molecular biology of the hepatitis B viruses. Annual Review of Biochemistry 56:651–693
     [Google Scholar]
  10. Gorman C. M., Moffatt 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]
  11. Gust I. D., Burrell C. J., Coulepis A. G., Robinson W. S., Zuckerman A. J. 1986; Taxonomic classification of human hepatitis B virus. Intervirology 25:14–29
     [Google Scholar]
  12. Hay N., Takimoto M., Bishop J. M. 1989; A FOS protein is present in a complex that binds a negative regulator of MYC. Genes and Development 3:293–303
     [Google Scholar]
  13. Hirsch R. C., Lavine J. E., Chang L., Varmus H. E., Ganem D. 1990; Polymerase gene products of hepatitis B viruses are required for genomic RNA packaging as well as for reverse transcription. Nature, London 344:552–555
     [Google Scholar]
  14. Hirt B. 1967; Selective extraction of polyoma DNA from infected mouse cell cultures. Journal of Molecular Biology 26:365–369
     [Google Scholar]
  15. Honigwachs J., Faktor O., Dikstein R., Shaul Y., Laub O. 1989; Liver-specific expression of hepatitis B virus is determined by the combined action of the core gene promoter and the enhancer. Journal of Virology 63:919–924
     [Google Scholar]
  16. Jameel S., Siddiqui A. 1986; The human hepatitis B virus enhancer requires trans-acting cellular factor(s) for activity. Molecular and Cellular Biology 6:710–715
     [Google Scholar]
  17. Kekule A. S., Lauer U., Meyer M., Caselmann W. H., Hofschneider P. H., Koshy R. 1990; The preS2/S region of integrated hepatitis B virus DNA encodes a transcriptional transactivator. Nature, London 343:457–461
     [Google Scholar]
  18. Koikeda S., Ibuki R., Sawada Y., Nagata K., Shibata H., Masamune Y., Nakanishi Y. 1990; Nuclear factor I stimulates transcription of the adenovirus 12 El A gene in a cell-free system. Biochimica et biophysica acta 1048:85–92
     [Google Scholar]
  19. Landschulz W. H., Johnson P. F., Adashi E. Y., Graves B. J., McKnight S. L. 1988; Isolation of a recombinant copy of the gene encoding C/EBP. Genes and Development 2:786–800
     [Google Scholar]
  20. Ostapchuk P., Scheirle G., Hearing P. 1989; Binding of nuclear factor EF-C to a functional domain of the hepatitis B virus enhancer region. Molecular and Cellular Biology 9:2787–2797
     [Google Scholar]
  21. Paonessa G., Gounari F., Frank R., Cortese R. 1988; Purification of a NFl-like DNA-binding protein from rat liver cloning of the corresponding cDNA. EMBO Journal 7:3115–3123
     [Google Scholar]
  22. Patel N. U., Jameel S., Isom H., Siddiqui A. 1989; Interactions between nuclear factors and the hepatitis B virus enhancer. Journal of Virology 63:5293–5301
     [Google Scholar]
  23. Pei D., Shih C. 1990; Transcriptional activation and repression by cellular DNA-binding protein C/EBP. Journal of Virology 64:1517–1522
     [Google Scholar]
  24. Radziwill G., Tucker W., Schaller H. 1990; Mutational analysis of the hepatitis B virus P gene product: domain structure and RNase H activity. Journal of Virology 64:613–620
     [Google Scholar]
  25. Seto E., Zhou D.-X., Peterlin B. M., Yen T. S. B. 1989; Transactivation by the hepatitis B virus X protein shows cell-type specificity. Virology 173:764–766
     [Google Scholar]
  26. Shaul Y., Ben-Levy R. 1987; Multiple nuclear proteins in liver cells are bound to hepatitis B virus enhancer element and its upstream sequences. EMBO Journal 6:1913–1920
     [Google Scholar]
  27. Shaul Y., Rutter W. J., Laub O. 1985; A human hepatitis B viral enhancer element. EMBO Journal 4:427–430
     [Google Scholar]
  28. Siddiqui A., Gaynor R., Srinivasan A., Mapoles J., Farr R. W. 1989; Trans-activation of viral enhancers including long terminal repeat of the human immunodeficiency virus by the hepatitis B virus X protein. Virology 169:479–484
     [Google Scholar]
  29. Spandau D. F., Lee C. H. 1987; The X protein of hepatitis B virus is a trans-activating factor. In Hepadnaviruses pp 31–46 Edited by Robinson W., Koiki K., Will H. New York:: Alan R. Liss;
     [Google Scholar]
  30. Spandau D. F., Lee C.-H. 1988; Trans-activation of viral enhancers by the hepatitis B virus X protein. Journal of Virology 62:427–434
     [Google Scholar]
  31. Tiollais P., Pourcel C., Dejean A. 1985; The hepatitis B virus. Nature, London 317:489–495
     [Google Scholar]
  32. Twu J.-S., Schloemer R. H. 1987; Transcriptional transactivating function of hepatitis B virus. Journal of Virology 61:3448–3453
     [Google Scholar]
  33. Twu J.-S., Schloemer R. H. 1989; Transcription of the human beta-interferon gene is inhibited by hepatitis B virus. Journal of Virology 63:3065–3071
     [Google Scholar]
  34. Twu J.-S., Lee C.-H., Lin P. M., Schloemer R. H. 1988; Hepatitis B virus suppresses expression of human beta-interferon. Proceedings of the National Academy of Sciences, U.S.A 85:252–256
     [Google Scholar]
  35. Yaginuma D., Koike K. 1989; Identification of a promoter region for 3-6-kilobase mRNA of hepatitis B virus and specific cellular binding protein. Journal of Virology 63:2914–2920
     [Google Scholar]
  36. Zahm P., Hofschneider P. H., Koshy R. 1988; The HBV X-ORF encodes a transactivator: a potential factor in viral hepatocarcino- genesis. Oncogene 3:169–177
     [Google Scholar]
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Repression of the hepatitis B virus enhancer by a cellular factor
J. Gen. Virol. 73, 131 (1992); https://doi.org/10.1099/0022-1317-73-1-131
/content/journal/jgv/10.1099/0022-1317-73-1-131
/content/journal/jgv/10.1099/0022-1317-73-1-131
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