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. 1990 Dec 25;18(24):7417–7423. doi: 10.1093/nar/18.24.7417

Regulation of a human neurotropic virus promoter, JCVE: identification of a novel activator domain located upstream from the 98 bp enhancer promoter region.

S Ahmed 1, M Chowdhury 1, K Khalili 1
PMCID: PMC332880  PMID: 2175435

Abstract

Transcription of the human neurotropic virus promoter, JCVE, and its regulation in glial cells are controlled by the 98 bp tandem repeats positioned between the viral early and late genes. Here, we show that a region, designated domain-D, located upstream from the 98 bp repeats functions as a transcriptional activator and increases JCVE promoter activity. Using the reporter SV40E promoter fused to the bacterial chloramphenicol acetyltransferase (CAT) gene, we demonstrate that domain-D stimulates the basal SV40E promoter activity in glial and to a lesser degree in HeLa cells. Results from gel mobility-shift assays indicate that domain-D interacts with proteins derived from glial and HeLa extracts and results in the formation of specific DNA-protein complexes. Through UV cross-linking assays, we demonstrate that these complexes have similar electrophoretic mobilities which comigrate with the 43-50 Kd proteins derived from glial and HeLa cells. These findings, together with our previous observations, imply that the JCVE control region is composed of multiple common and specific activator domains that may account for the increased expression of the promoter in glial cells. The possible role of the D-binding protein in transcription of the JCVE promoter is discussed.

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Selected References

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

  1. ASTROM K. E., MANCALL E. L., RICHARDSON E. P., Jr Progressive multifocal leuko-encephalopathy; a hitherto unrecognized complication of chronic lymphatic leukaemia and Hodgkin's disease. Brain. 1958 Mar;81(1):93–111. doi: 10.1093/brain/81.1.93. [DOI] [PubMed] [Google Scholar]
  2. Ahmed S., Rappaport J., Tada H., Kerr D., Khalili K. A nuclear protein derived from brain cells stimulates transcription of the human neurotropic virus promoter, JCVE, in vitro. J Biol Chem. 1990 Aug 15;265(23):13899–13905. [PubMed] [Google Scholar]
  3. Banerji J., Olson L., Schaffner W. A lymphocyte-specific cellular enhancer is located downstream of the joining region in immunoglobulin heavy chain genes. Cell. 1983 Jul;33(3):729–740. doi: 10.1016/0092-8674(83)90015-6. [DOI] [PubMed] [Google Scholar]
  4. Dynan W. S., Tjian R. Control of eukaryotic messenger RNA synthesis by sequence-specific DNA-binding proteins. 1985 Aug 29-Sep 4Nature. 316(6031):774–778. doi: 10.1038/316774a0. [DOI] [PubMed] [Google Scholar]
  5. Feigenbaum L., Khalili K., Major E., Khoury G. Regulation of the host range of human papovavirus JCV. Proc Natl Acad Sci U S A. 1987 Jun;84(11):3695–3698. doi: 10.1073/pnas.84.11.3695. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Frisque R. J., Bream G. L., Cannella M. T. Human polyomavirus JC virus genome. J Virol. 1984 Aug;51(2):458–469. doi: 10.1128/jvi.51.2.458-469.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Frisque R. J., Rifkin D. B., Walker D. L. Transformation of primary hamster brain cells with JC virus and its DNA. J Virol. 1980 Jul;35(1):265–269. doi: 10.1128/jvi.35.1.265-269.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Garner M. M., Revzin A. A gel electrophoresis method for quantifying the binding of proteins to specific DNA regions: application to components of the Escherichia coli lactose operon regulatory system. Nucleic Acids Res. 1981 Jul 10;9(13):3047–3060. doi: 10.1093/nar/9.13.3047. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gorman C. M., Merlino G. T., Willingham M. C., Pastan I., Howard B. H. The Rous sarcoma virus long terminal repeat is a strong promoter when introduced into a variety of eukaryotic cells by DNA-mediated transfection. Proc Natl Acad Sci U S A. 1982 Nov;79(22):6777–6781. doi: 10.1073/pnas.79.22.6777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. Graham F. L., van der Eb A. J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. doi: 10.1016/0042-6822(73)90341-3. [DOI] [PubMed] [Google Scholar]
  12. Johnson P. F., Landschulz W. H., Graves B. J., McKnight S. L. Identification of a rat liver nuclear protein that binds to the enhancer core element of three animal viruses. Genes Dev. 1987 Apr;1(2):133–146. doi: 10.1101/gad.1.2.133. [DOI] [PubMed] [Google Scholar]
  13. Johnson R. T. Evidence for polyomaviruses in human neurological diseases. Prog Clin Biol Res. 1983;105:183–190. [PubMed] [Google Scholar]
  14. Kenney S., Natarajan V., Strike D., Khoury G., Salzman N. P. JC virus enhancer-promoter active in human brain cells. Science. 1984 Dec 14;226(4680):1337–1339. doi: 10.1126/science.6095453. [DOI] [PubMed] [Google Scholar]
  15. Khalili K., Feigenbaum L., Khoury G. Evidence for a shift in 5'-termini of early viral RNA during the lytic cycle of JC virus. Virology. 1987 Jun;158(2):469–472. doi: 10.1016/0042-6822(87)90224-8. [DOI] [PubMed] [Google Scholar]
  16. Khalili K., Rappaport J., Khoury G. Nuclear factors in human brain cells bind specifically to the JCV regulatory region. EMBO J. 1988 Apr;7(4):1205–1210. doi: 10.1002/j.1460-2075.1988.tb02932.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Khoury G., Gruss P. Enhancer elements. Cell. 1983 Jun;33(2):313–314. doi: 10.1016/0092-8674(83)90410-5. [DOI] [PubMed] [Google Scholar]
  18. Laimins L. A., Khoury G., Gorman C., Howard B., Gruss P. Host-specific activation of transcription by tandem repeats from simian virus 40 and Moloney murine sarcoma virus. Proc Natl Acad Sci U S A. 1982 Nov;79(21):6453–6457. doi: 10.1073/pnas.79.21.6453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lenardo M., Pierce J. W., Baltimore D. Protein-binding sites in Ig gene enhancers determine transcriptional activity and inducibility. Science. 1987 Jun 19;236(4808):1573–1577. doi: 10.1126/science.3109035. [DOI] [PubMed] [Google Scholar]
  20. Maniatis T., Goodbourn S., Fischer J. A. Regulation of inducible and tissue-specific gene expression. Science. 1987 Jun 5;236(4806):1237–1245. doi: 10.1126/science.3296191. [DOI] [PubMed] [Google Scholar]
  21. Manley J. L., Fire A., Samuels M., Sharp P. A. In vitro transcription: whole-cell extract. Methods Enzymol. 1983;101:568–582. doi: 10.1016/0076-6879(83)01038-1. [DOI] [PubMed] [Google Scholar]
  22. Maxam A. M., Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. doi: 10.1016/s0076-6879(80)65059-9. [DOI] [PubMed] [Google Scholar]
  23. McKnight S., Tjian R. Transcriptional selectivity of viral genes in mammalian cells. Cell. 1986 Sep 12;46(6):795–805. doi: 10.1016/0092-8674(86)90061-9. [DOI] [PubMed] [Google Scholar]
  24. Norton P. A., Coffin J. M. Bacterial beta-galactosidase as a marker of Rous sarcoma virus gene expression and replication. Mol Cell Biol. 1985 Feb;5(2):281–290. doi: 10.1128/mcb.5.2.281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Padgett B. L., Rogers C. M., Walker D. L. JC virus, a human polyomavirus associated with progressive multifocal leukoencephalopathy: additional biological characteristics and antigenic relationships. Infect Immun. 1977 Feb;15(2):656–662. doi: 10.1128/iai.15.2.656-662.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Padgett B. L., Walker D. L., ZuRhein G. M., Eckroade R. J., Dessel B. H. Cultivation of papova-like virus from human brain with progressive multifocal leucoencephalopathy. Lancet. 1971 Jun 19;1(7712):1257–1260. doi: 10.1016/s0140-6736(71)91777-6. [DOI] [PubMed] [Google Scholar]
  27. Ptashne M. How eukaryotic transcriptional activators work. Nature. 1988 Oct 20;335(6192):683–689. doi: 10.1038/335683a0. [DOI] [PubMed] [Google Scholar]
  28. RICHARDSON E. P., Jr Progressive multifocal leukoencephalopathy. N Engl J Med. 1961 Oct 26;265:815–823. doi: 10.1056/NEJM196110262651701. [DOI] [PubMed] [Google Scholar]
  29. Sassone-Corsi P., Corden J., Kédinger C., Chambon P. Promotion of specific in vitro transcription by excised "TATA" box sequences inserted in a foreign nucleotide environment. Nucleic Acids Res. 1981 Aug 25;9(16):3941–3958. doi: 10.1093/nar/9.16.3941. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. 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]
  31. Tada H., Lashgari M., Rappaport J., Khalili K. Cell type-specific expression of JC virus early promoter is determined by positive and negative regulation. J Virol. 1989 Jan;63(1):463–466. doi: 10.1128/jvi.63.1.463-466.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]

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