Skip to main content
NCBI home page
The EMBO Journal logoLink to The EMBO Journal
. 1987 Jul;6(7):1913–1920. doi: 10.1002/j.1460-2075.1987.tb02451.x

Multiple nuclear proteins in liver cells are bound to hepatitis B virus enhancer element and its upstream sequences.

Y Shaul 1, R Ben-Levy 1
PMCID: PMC553576  PMID: 3653073

Abstract

The transcriptional enhancer element in the hepatitis B virus (HBV) genome displays tissue-specific activity, suggesting that this element interacts with cellular specific factors. Using a nitrocellulose filter binding assay and DNase I footprinting, we have found that liver cell-specific nuclear proteins are bound to the HBV enhancer element (the E site) and its adjacent sequences. Four DNase I-protected sites were revealed, all contain a sequence motif resembling the sequence of the SV40 enhancer core element. Evidence is provided to show that: (i) these sites are protected by at least three distinct nuclear proteins and (ii) the presence of some of these proteins is dependent on the differentiation stage of the liver cells. Interestingly an octamer sequence found in the E site appears also in the promoter region of several liver-specific genes, which suggests that the E site and its corresponding binding protein(s) determine the tissue-specific expression of the HBV enhancer element.

Full text

PDF
1913

Images in this article

1914Fig. 1.
on p.1914
1914Fig. 2.
on p.1914
1915Fig. 3.
on p.1915
1915Fig. 4.
on p.1915
1916Fig. 5.
on p.1916
1916Fig. 6.
on p.1916
1917Fig. 7.
on p.1917
1917Fig. 8.
on p.1917

Selected References

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

  1. Böhnlein E., Gruss P. Interaction of distinct nuclear proteins with sequences controlling the expression of polyomavirus early genes. Mol Cell Biol. 1986 May;6(5):1401–1411. doi: 10.1128/mcb.6.5.1401. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Chang C., Lin Y., O-Lee T. W., Chou C. K., Lee T. S., Liu T. J., P'eng F. K., Chen T. Y., Hu C. P. Induction of plasma protein secretion in a newly established human hepatoma cell line. Mol Cell Biol. 1983 Jun;3(6):1133–1137. doi: 10.1128/mcb.3.6.1133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Church G. M., Ephrussi A., Gilbert W., Tonegawa S. Cell-type-specific contacts to immunoglobulin enhancers in nuclei. 1985 Feb 28-Mar 6Nature. 313(6005):798–801. doi: 10.1038/313798a0. [DOI] [PubMed] [Google Scholar]
  4. Ciliberto G., Dente L., Cortese R. Cell-specific expression of a transfected human alpha 1-antitrypsin gene. Cell. 1985 Jun;41(2):531–540. doi: 10.1016/s0092-8674(85)80026-x. [DOI] [PubMed] [Google Scholar]
  5. Davidson I., Fromental C., Augereau P., Wildeman A., Zenke M., Chambon P. Cell-type specific protein binding to the enhancer of simian virus 40 in nuclear extracts. Nature. 1986 Oct 9;323(6088):544–548. doi: 10.1038/323544a0. [DOI] [PubMed] [Google Scholar]
  6. Desplan C., Theis J., O'Farrell P. H. The Drosophila developmental gene, engrailed, encodes a sequence-specific DNA binding activity. Nature. 1985 Dec 19;318(6047):630–635. doi: 10.1038/318630a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Ephrussi A., Church G. M., Tonegawa S., Gilbert W. B lineage--specific interactions of an immunoglobulin enhancer with cellular factors in vivo. Science. 1985 Jan 11;227(4683):134–140. doi: 10.1126/science.3917574. [DOI] [PubMed] [Google Scholar]
  8. Galas D. J., Schmitz A. DNAse footprinting: a simple method for the detection of protein-DNA binding specificity. Nucleic Acids Res. 1978 Sep;5(9):3157–3170. doi: 10.1093/nar/5.9.3157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gehring W. J. The homeo box: a key to the understanding of development? Cell. 1985 Jan;40(1):3–5. doi: 10.1016/0092-8674(85)90300-9. [DOI] [PubMed] [Google Scholar]
  10. Godbout R., Ingram R., Tilghman S. M. Multiple regulatory elements in the intergenic region between the alpha-fetoprotein and albumin genes. Mol Cell Biol. 1986 Feb;6(2):477–487. doi: 10.1128/mcb.6.2.477. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Herr W., Clarke J. The SV40 enhancer is composed of multiple functional elements that can compensate for one another. Cell. 1986 May 9;45(3):461–470. doi: 10.1016/0092-8674(86)90332-6. [DOI] [PubMed] [Google Scholar]
  13. Jameel S., Siddiqui A. The human hepatitis B virus enhancer requires trans-acting cellular factor(s) for activity. Mol Cell Biol. 1986 Feb;6(2):710–715. doi: 10.1128/mcb.6.2.710. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Knowles B. B., Howe C. C., Aden D. P. Human hepatocellular carcinoma cell lines secrete the major plasma proteins and hepatitis B surface antigen. Science. 1980 Jul 25;209(4455):497–499. doi: 10.1126/science.6248960. [DOI] [PubMed] [Google Scholar]
  15. Landolfi N. F., Capra J. D., Tucker P. W. Interaction of cell-type-specific nuclear proteins with immunoglobulin VH promoter region sequences. Nature. 1986 Oct 9;323(6088):548–551. doi: 10.1038/323548a0. [DOI] [PubMed] [Google Scholar]
  16. MacNab G. M., Alexander J. J., Lecatsas G., Bey E. M., Urbanowicz J. M. Hepatitis B surface antigen produced by a human hepatoma cell line. Br J Cancer. 1976 Nov;34(5):509–515. doi: 10.1038/bjc.1976.205. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Ohlsson H., Edlund T. Sequence-specific interactions of nuclear factors with the insulin gene enhancer. Cell. 1986 Apr 11;45(1):35–44. doi: 10.1016/0092-8674(86)90535-0. [DOI] [PubMed] [Google Scholar]
  18. Ostapchuk P., Diffley J. F., Bruder J. T., Stillman B., Levine A. J., Hearing P. Interaction of a nuclear factor with the polyomavirus enhancer region. Proc Natl Acad Sci U S A. 1986 Nov;83(22):8550–8554. doi: 10.1073/pnas.83.22.8550. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Piette J., Kryszke M. H., Yaniv M. Specific interaction of cellular factors with the B enhancer of polyoma virus. EMBO J. 1985 Oct;4(10):2675–2685. doi: 10.1002/j.1460-2075.1985.tb03987.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Pourcel C., Louise A., Gervais M., Chenciner N., Dubois M. F., Tiollais P. Transcription of the hepatitis B surface antigen gene in mouse cells transformed with cloned viral DNA. J Virol. 1982 Apr;42(1):100–105. doi: 10.1128/jvi.42.1.100-105.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Ptashne M. Gene regulation by proteins acting nearby and at a distance. Nature. 1986 Aug 21;322(6081):697–701. doi: 10.1038/322697a0. [DOI] [PubMed] [Google Scholar]
  22. Riggs A. D., Bourgeois S., Cohn M. The lac repressor-operator interaction. 3. Kinetic studies. J Mol Biol. 1970 Nov 14;53(3):401–417. doi: 10.1016/0022-2836(70)90074-4. [DOI] [PubMed] [Google Scholar]
  23. Sassone-Corsi P., Wildeman A., Chambon P. A trans-acting factor is responsible for the simian virus 40 enhancer activity in vitro. Nature. 1985 Feb 7;313(6002):458–463. doi: 10.1038/313458a0. [DOI] [PubMed] [Google Scholar]
  24. Schöler H. R., Gruss P. Specific interaction between enhancer-containing molecules and cellular components. Cell. 1984 Feb;36(2):403–411. doi: 10.1016/0092-8674(84)90233-2. [DOI] [PubMed] [Google Scholar]
  25. Sen R., Baltimore D. Multiple nuclear factors interact with the immunoglobulin enhancer sequences. Cell. 1986 Aug 29;46(5):705–716. doi: 10.1016/0092-8674(86)90346-6. [DOI] [PubMed] [Google Scholar]
  26. Shaul Y., Ben-Levy R., De-Medina T. High affinity binding site for nuclear factor I next to the hepatitis B virus S gene promoter. EMBO J. 1986 Aug;5(8):1967–1971. doi: 10.1002/j.1460-2075.1986.tb04451.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Shaul Y., Rutter W. J., Laub O. A human hepatitis B viral enhancer element. EMBO J. 1985 Feb;4(2):427–430. doi: 10.1002/j.1460-2075.1985.tb03646.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Siebenlist U., Hennighausen L., Battey J., Leder P. Chromatin structure and protein binding in the putative regulatory region of the c-myc gene in Burkitt lymphoma. Cell. 1984 Jun;37(2):381–391. doi: 10.1016/0092-8674(84)90368-4. [DOI] [PubMed] [Google Scholar]
  29. Singh H., Sen R., Baltimore D., Sharp P. A. A nuclear factor that binds to a conserved sequence motif in transcriptional control elements of immunoglobulin genes. Nature. 1986 Jan 9;319(6049):154–158. doi: 10.1038/319154a0. [DOI] [PubMed] [Google Scholar]
  30. Staudt L. M., Singh H., Sen R., Wirth T., Sharp P. A., Baltimore D. A lymphoid-specific protein binding to the octamer motif of immunoglobulin genes. Nature. 1986 Oct 16;323(6089):640–643. doi: 10.1038/323640a0. [DOI] [PubMed] [Google Scholar]
  31. Tognoni A., Cattaneo R., Serfling E., Schaffner W. A novel expression selection approach allows precise mapping of the hepatitis B virus enhancer. Nucleic Acids Res. 1985 Oct 25;13(20):7457–7472. doi: 10.1093/nar/13.20.7457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Tur-Kaspa R., Burk R. D., Shaul Y., Shafritz D. A. Hepatitis B virus DNA contains a glucocorticoid-responsive element. Proc Natl Acad Sci U S A. 1986 Mar;83(6):1627–1631. doi: 10.1073/pnas.83.6.1627. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Weiher H., König M., Gruss P. Multiple point mutations affecting the simian virus 40 enhancer. Science. 1983 Feb 11;219(4585):626–631. doi: 10.1126/science.6297005. [DOI] [PubMed] [Google Scholar]
  34. Weinberger J., Baltimore D., Sharp P. A. Distinct factors bind to apparently homologous sequences in the immunoglobulin heavy-chain enhancer. 1986 Aug 28-Sep 3Nature. 322(6082):846–848. doi: 10.1038/322846a0. [DOI] [PubMed] [Google Scholar]
  35. Wildeman A. G., Sassone-Corsi P., Grundström T., Zenke M., Chambon P. Stimulation of in vitro transcription from the SV40 early promoter by the enhancer involves a specific trans-acting factor. EMBO J. 1984 Dec 20;3(13):3129–3133. doi: 10.1002/j.1460-2075.1984.tb02269.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Wildeman A. G., Zenke M., Schatz C., Wintzerith M., Grundström T., Matthes H., Takahashi K., Chambon P. Specific protein binding to the simian virus 40 enhancer in vitro. Mol Cell Biol. 1986 Jun;6(6):2098–2105. doi: 10.1128/mcb.6.6.2098. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Zenke M., Grundström T., Matthes H., Wintzerith M., Schatz C., Wildeman A., Chambon P. Multiple sequence motifs are involved in SV40 enhancer function. EMBO J. 1986 Feb;5(2):387–397. doi: 10.1002/j.1460-2075.1986.tb04224.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES