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. 1990 Jul;64(7):3185–3191. doi: 10.1128/jvi.64.7.3185-3191.1990

Enhancer functions in U3 of Akv virus: a role for cooperativity of a tandem repeat unit and its flanking DNA sequences.

S Lovmand 1, N O Kjeldgaard 1, P Jørgensen 1, F S Pedersen 1
PMCID: PMC249523  PMID: 2161937

Abstract

cis-Acting transcriptional control elements in the U3 region of the murine retrovirus Akv were analyzed in mouse NIH 3T3 fibroblast cells by using a transient expression vector system based upon a complete long terminal repeat with linked flanking sequences. Deletion analysis pointed to the essential role of sequences within the 99-base-pair direct repeats, and a fragment encompassing the two repeats was found to possess orientation-independent enhancer activity when positioned either upstream or downstream of the transcriptional unit. Removal of one copy of the 99-base-pair repeat led to a reduction in activity of about 2.5-fold when located in an intact U3 environment but to reductions of up to 2 orders of magnitude when placed in other sequence contexts. Our studies of enhancer functions in the presence of one versus two copies of the tandem repeat point to duplicate functions of repeat sequences and sequences flanking the repeat region and emphasize the complex overall organization of this U3 region.

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Selected References

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

  1. An G., Hidaka K., Siminovitch L. Expression of bacterial beta-galactosidase in animal cells. Mol Cell Biol. 1982 Dec;2(12):1628–1632. doi: 10.1128/mcb.2.12.1628. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Boral A. L., Okenquist S. A., Lenz J. Identification of the SL3-3 virus enhancer core as a T-lymphoma cell-specific element. J Virol. 1989 Jan;63(1):76–84. doi: 10.1128/jvi.63.1.76-84.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Borgmeyer U., Nowock J., Sippel A. E. The TGGCA-binding protein: a eukaryotic nuclear protein recognizing a symmetrical sequence on double-stranded linear DNA. Nucleic Acids Res. 1984 May 25;12(10):4295–4311. doi: 10.1093/nar/12.10.4295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Celander D., Haseltine W. A. Glucocorticoid regulation of murine leukemia virus transcription elements is specified by determinants within the viral enhancer region. J Virol. 1987 Feb;61(2):269–275. doi: 10.1128/jvi.61.2.269-275.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Celander D., Haseltine W. A. Tissue-specific transcription preference as a determinant of cell tropism and leukaemogenic potential of murine retroviruses. Nature. 1984 Nov 8;312(5990):159–162. doi: 10.1038/312159a0. [DOI] [PubMed] [Google Scholar]
  6. Chen H. R., Barker W. C. Nucleotide sequences of the retroviral long terminal repeats and their adjacent regions. Nucleic Acids Res. 1984 Feb 24;12(4):1767–1778. doi: 10.1093/nar/12.4.1767. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Corcoran L. M., Adams J. M., Dunn A. R., Cory S. Murine T lymphomas in which the cellular myc oncogene has been activated by retroviral insertion. Cell. 1984 May;37(1):113–122. doi: 10.1016/0092-8674(84)90306-4. [DOI] [PubMed] [Google Scholar]
  8. Dai H. Y., Etzerodt M., Baekgaard A. J., Lovmand S., Jørgensen P., Kjeldgaard N. O., Pedersen F. S. Multiple sequence elements in the U3 region of the leukemogenic murine retrovirus SL3-2 contribute to cell-dependent gene expression. Virology. 1990 Apr;175(2):581–585. doi: 10.1016/0042-6822(90)90445-w. [DOI] [PubMed] [Google Scholar]
  9. Davidson I., Xiao J. H., Rosales R., Staub A., Chambon P. The HeLa cell protein TEF-1 binds specifically and cooperatively to two SV40 enhancer motifs of unrelated sequence. Cell. 1988 Sep 23;54(7):931–942. doi: 10.1016/0092-8674(88)90108-0. [DOI] [PubMed] [Google Scholar]
  10. DesGroseillers L., Villemur R., Jolicoeur P. The high leukemogenic potential of Gross passage A murine leukemia virus maps in the region of the genome corresponding to the long terminal repeat and to the 3' end of env. J Virol. 1983 Jul;47(1):24–32. doi: 10.1128/jvi.47.1.24-32.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Etzerodt M., Mikkelsen T., Pedersen F. S., Kjeldgaard N. O., Jørgensen P. The nucleotide sequence of the Akv murine leukemia virus genome. Virology. 1984 Apr 15;134(1):196–207. doi: 10.1016/0042-6822(84)90285-x. [DOI] [PubMed] [Google Scholar]
  12. Flanagan J. R., Krieg A. M., Max E. E., Khan A. S. Negative control region at the 5' end of murine leukemia virus long terminal repeats. Mol Cell Biol. 1989 Feb;9(2):739–746. doi: 10.1128/mcb.9.2.739. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. 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]
  15. Graves B. J., Eisenman R. N., McKnight S. L. Delineation of transcriptional control signals within the Moloney murine sarcoma virus long terminal repeat. Mol Cell Biol. 1985 Aug;5(8):1948–1958. doi: 10.1128/mcb.5.8.1948. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hall C. V., Jacob P. E., Ringold G. M., Lee F. Expression and regulation of Escherichia coli lacZ gene fusions in mammalian cells. J Mol Appl Genet. 1983;2(1):101–109. [PubMed] [Google Scholar]
  17. Hallberg B., Grundström T. Tissue specific sequence motifs in the enhancer of the leukaemogenic mouse retrovirus SL3-3. Nucleic Acids Res. 1988 Jul 11;16(13):5927–5944. doi: 10.1093/nar/16.13.5927. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hattori M., Sakaki Y. Dideoxy sequencing method using denatured plasmid templates. Anal Biochem. 1986 Feb 1;152(2):232–238. doi: 10.1016/0003-2697(86)90403-3. [DOI] [PubMed] [Google Scholar]
  19. Herbomel P., Bourachot B., Yaniv M. Two distinct enhancers with different cell specificities coexist in the regulatory region of polyoma. Cell. 1984 Dec;39(3 Pt 2):653–662. doi: 10.1016/0092-8674(84)90472-0. [DOI] [PubMed] [Google Scholar]
  20. Herr W. Nucleotide sequence of AKV murine leukemia virus. J Virol. 1984 Feb;49(2):471–478. doi: 10.1128/jvi.49.2.471-478.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Imagawa M., Chiu R., Karin M. Transcription factor AP-2 mediates induction by two different signal-transduction pathways: protein kinase C and cAMP. Cell. 1987 Oct 23;51(2):251–260. doi: 10.1016/0092-8674(87)90152-8. [DOI] [PubMed] [Google Scholar]
  22. Jones K. A., Kadonaga J. T., Rosenfeld P. J., Kelly T. J., Tjian R. A cellular DNA-binding protein that activates eukaryotic transcription and DNA replication. Cell. 1987 Jan 16;48(1):79–89. doi: 10.1016/0092-8674(87)90358-8. [DOI] [PubMed] [Google Scholar]
  23. Laimins L. A., Gruss P., Pozzatti R., Khoury G. Characterization of enhancer elements in the long terminal repeat of Moloney murine sarcoma virus. J Virol. 1984 Jan;49(1):183–189. doi: 10.1128/jvi.49.1.183-189.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Leib-Mösch C., Schmidt J., Etzerodt M., Pedersen F. S., Hehlmann R., Erfle V. Oncogenic retrovirus from spontaneous murine osteomas. II. Molecular cloning and genomic characterization. Virology. 1986 Apr 15;150(1):96–105. doi: 10.1016/0042-6822(86)90269-2. [DOI] [PubMed] [Google Scholar]
  25. Lenz J., Celander D., Crowther R. L., Patarca R., Perkins D. W., Haseltine W. A. Determination of the leukaemogenicity of a murine retrovirus by sequences within the long terminal repeat. 1984 Mar 29-Apr 4Nature. 308(5958):467–470. doi: 10.1038/308467a0. [DOI] [PubMed] [Google Scholar]
  26. Lenz J., Crowther R., Straceski A., Haseltine W. Nucleotide sequence of the Akv env gene. J Virol. 1982 May;42(2):519–529. doi: 10.1128/jvi.42.2.519-529.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Lichtsteiner S., Wuarin J., Schibler U. The interplay of DNA-binding proteins on the promoter of the mouse albumin gene. Cell. 1987 Dec 24;51(6):963–973. doi: 10.1016/0092-8674(87)90583-6. [DOI] [PubMed] [Google Scholar]
  28. LoSardo J. E., Cupelli L. A., Short M. K., Berman J. W., Lenz J. Differences in activities of murine retroviral long terminal repeats in cytotoxic T lymphocytes and T-lymphoma cells. J Virol. 1989 Mar;63(3):1087–1094. doi: 10.1128/jvi.63.3.1087-1094.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Lopata M. A., Cleveland D. W., Sollner-Webb B. High level transient expression of a chloramphenicol acetyl transferase gene by DEAE-dextran mediated DNA transfection coupled with a dimethyl sulfoxide or glycerol shock treatment. Nucleic Acids Res. 1984 Jul 25;12(14):5707–5717. doi: 10.1093/nar/12.14.5707. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Miksicek R., Heber A., Schmid W., Danesch U., Posseckert G., Beato M., Schütz G. Glucocorticoid responsiveness of the transcriptional enhancer of Moloney murine sarcoma virus. Cell. 1986 Jul 18;46(2):283–290. doi: 10.1016/0092-8674(86)90745-2. [DOI] [PubMed] [Google Scholar]
  31. Mitchell P. J., Wang C., Tjian R. Positive and negative regulation of transcription in vitro: enhancer-binding protein AP-2 is inhibited by SV40 T antigen. Cell. 1987 Sep 11;50(6):847–861. doi: 10.1016/0092-8674(87)90512-5. [DOI] [PubMed] [Google Scholar]
  32. Paludan K., Dai H. Y., Duch M., Jørgensen P., Kjeldgaard N. O., Pedersen F. S. Different relative expression from two murine leukemia virus long terminal repeats in unintegrated transfected DNA and in integrated retroviral vector proviruses. J Virol. 1989 Dec;63(12):5201–5207. doi: 10.1128/jvi.63.12.5201-5207.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Scheidereit C., Beato M. Contacts between hormone receptor and DNA double helix within a glucocorticoid regulatory element of mouse mammary tumor virus. Proc Natl Acad Sci U S A. 1984 May;81(10):3029–3033. doi: 10.1073/pnas.81.10.3029. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Schulze F., Boehnlein E., Gruss P. Mutational analyses of the Moloney murine sarcoma virus enhancer. DNA. 1985 Jun;4(3):193–202. doi: 10.1089/dna.1985.4.193. [DOI] [PubMed] [Google Scholar]
  35. Shinnick T. M., Lerner R. A., Sutcliffe J. G. Nucleotide sequence of Moloney murine leukaemia virus. Nature. 1981 Oct 15;293(5833):543–548. doi: 10.1038/293543a0. [DOI] [PubMed] [Google Scholar]
  36. Short M. K., Okenquist S. A., Lenz J. Correlation of leukemogenic potential of murine retroviruses with transcriptional tissue preference of the viral long terminal repeats. J Virol. 1987 Apr;61(4):1067–1072. doi: 10.1128/jvi.61.4.1067-1072.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Soberon X., Covarrubias L., Bolivar F. Construction and characterization of new cloning vehicles. IV. Deletion derivatives of pBR322 and pBR325. Gene. 1980 May;9(3-4):287–305. doi: 10.1016/0378-1119(90)90328-o. [DOI] [PubMed] [Google Scholar]
  38. Speck N. A., Baltimore D. Six distinct nuclear factors interact with the 75-base-pair repeat of the Moloney murine leukemia virus enhancer. Mol Cell Biol. 1987 Mar;7(3):1101–1110. doi: 10.1128/mcb.7.3.1101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Thornell A., Hallberg B., Grundström T. Differential protein binding in lymphocytes to a sequence in the enhancer of the mouse retrovirus SL3-3. Mol Cell Biol. 1988 Apr;8(4):1625–1637. doi: 10.1128/mcb.8.4.1625. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Van Beveren C., Enami S., Curran T., Verma I. M. FBR murine osteosarcoma virus. II. Nucleotide sequence of the provirus reveals that the genome contains sequences acquired from two cellular genes. Virology. 1984 May;135(1):229–243. doi: 10.1016/0042-6822(84)90133-8. [DOI] [PubMed] [Google Scholar]
  41. Van Beveren C., Rands E., Chattopadhyay S. K., Lowy D. R., Verma I. M. Long terminal repeat of murine retroviral DNAs: sequence analysis, host-proviral junctions, and preintegration site. J Virol. 1982 Feb;41(2):542–556. doi: 10.1128/jvi.41.2.542-556.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Van Beveren C., van Straaten F., Curran T., Müller R., Verma I. M. Analysis of FBJ-MuSV provirus and c-fos (mouse) gene reveals that viral and cellular fos gene products have different carboxy termini. Cell. 1983 Apr;32(4):1241–1255. doi: 10.1016/0092-8674(83)90306-9. [DOI] [PubMed] [Google Scholar]
  43. Villemur R., Rassart E., DesGroseillers L., Jolicoeur P. Molecular cloning of viral DNA from leukemogenic Gross passage A murine leukemia virus and nucleotide sequence of its long terminal repeat. J Virol. 1983 Feb;45(2):539–546. doi: 10.1128/jvi.45.2.539-546.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Williams T., Admon A., Lüscher B., Tjian R. Cloning and expression of AP-2, a cell-type-specific transcription factor that activates inducible enhancer elements. Genes Dev. 1988 Dec;2(12A):1557–1569. doi: 10.1101/gad.2.12a.1557. [DOI] [PubMed] [Google Scholar]
  45. Yoshimura F. K., Davison B., Chaffin K. Murine leukemia virus long terminal repeat sequences can enhance gene activity in a cell-type-specific manner. Mol Cell Biol. 1985 Oct;5(10):2832–2835. doi: 10.1128/mcb.5.10.2832. [DOI] [PMC free article] [PubMed] [Google Scholar]

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