Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1993 Mar;67(3):1545–1554. doi: 10.1128/jvi.67.3.1545-1554.1993

Functional and defective components of avian endogenous virus long terminal repeat enhancer sequences.

D E Habel 1, K L Dohrer 1, K F Conklin 1
PMCID: PMC237525  PMID: 8382309

Abstract

Oncogenic avian retroviruses, such as Rous sarcoma virus (RSV) and the avian leukosis viruses, contain a strong enhancer in the U3 portion of the proviral long terminal repeat (LTR). The LTRs of a second class of avian retroviruses, the endogenous viruses (ev) lack detectable enhancer activity. By creating ev-RSV hybrid LTRs, we previously demonstrated that, despite the lack of independent enhancer activity in the ev U3 region, ev LTRs contain sequences that are able to functionally replace essential enhancer domains from the RSV enhancer. A hypothesis proposed to explain these data was that ev LTRs contain a partial enhancer that includes sequences necessary but not sufficient for enhancer activity and that these sequences were complemented by RSV enhancer domains present in the original hybrid constructs to generate a functional enhancer. Studies described in this report were designed to define sequences from both the ev and RSV LTRs required to generate this composite enhancer. This was approached by generating additional ev-RSV hybrid LTRs that exchanged defined regions between ev and RSV and by directly testing the requirement for specific motifs by site-directed mutagenesis. Results obtained demonstrate that ev enhancer sequences are present in the same relative location as upstream enhancer sequences from RSV, with which they share limited sequence similarity. In addition, a 67-bp region from the internal portion of the RSV LTR that is required to complement ev enhancer sequences was identified. Finally, data showing that CArG motifs are essential for high-level activity, a finding that has not been previously demonstrated for retroviral LTRs, are presented.

Full text

PDF
1547

Images in this article

1549Image
on p.1549
1550Image
on p.1550
1551Image
on p.1551
1552Image
on p.1552

Selected References

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

  1. Astrin S. M., Robinson H. L., Crittenden L. B., Buss E. G., Wyban J., Hayward W. S. Ten genetic loci in the chicken that contain structural genes for endogenous avian leukosis viruses. Cold Spring Harb Symp Quant Biol. 1980;44(Pt 2):1105–1109. doi: 10.1101/sqb.1980.044.01.119. [DOI] [PubMed] [Google Scholar]
  2. Boulden A., Sealy L. Identification of a third protein factor which binds to the Rous sarcoma virus LTR enhancer: possible homology with the serum response factor. Virology. 1990 Jan;174(1):204–216. doi: 10.1016/0042-6822(90)90069-4. [DOI] [PubMed] [Google Scholar]
  3. Boxer L. M., Prywes R., Roeder R. G., Kedes L. The sarcomeric actin CArG-binding factor is indistinguishable from the c-fos serum response factor. Mol Cell Biol. 1989 Feb;9(2):515–522. doi: 10.1128/mcb.9.2.515. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Conklin K. F. Activation of an endogenous retrovirus enhancer by insertion into a heterologous context. J Virol. 1991 May;65(5):2525–2532. doi: 10.1128/jvi.65.5.2525-2532.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Crittenden L. B., Witter R. L., Fadly A. M. Low incidence of lymphoid tumors in chickens continuously producing endogenous virus. Avian Dis. 1979 Jul-Sep;23(3):646–653. [PubMed] [Google Scholar]
  6. Cullen B. R., Raymond K., Ju G. Functional analysis of the transcription control region located within the avian retroviral long terminal repeat. Mol Cell Biol. 1985 Mar;5(3):438–447. doi: 10.1128/mcb.5.3.438. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cullen B. R., Raymond K., Ju G. Transcriptional activity of avian retroviral long terminal repeats directly correlates with enhancer activity. J Virol. 1985 Feb;53(2):515–521. doi: 10.1128/jvi.53.2.515-521.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cullen B. R., Skalka A. M., Ju G. Endogenous avian retroviruses contain deficient promoter and leader sequences. Proc Natl Acad Sci U S A. 1983 May;80(10):2946–2950. doi: 10.1073/pnas.80.10.2946. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Cullen B. R. Trans-activation of human immunodeficiency virus occurs via a bimodal mechanism. Cell. 1986 Sep 26;46(7):973–982. doi: 10.1016/0092-8674(86)90696-3. [DOI] [PubMed] [Google Scholar]
  10. Dalton S., Treisman R. Characterization of SAP-1, a protein recruited by serum response factor to the c-fos serum response element. Cell. 1992 Feb 7;68(3):597–612. doi: 10.1016/0092-8674(92)90194-h. [DOI] [PubMed] [Google Scholar]
  11. Faber M., Sealy L. Rous sarcoma virus enhancer factor I is a ubiquitous CCAAT transcription factor highly related to CBF and NF-Y. J Biol Chem. 1990 Dec 25;265(36):22243–22254. [PubMed] [Google Scholar]
  12. Gilmartin G. M., Parsons J. T. Identification of transcriptional elements within the long terminal repeat of Rous sarcoma virus. Mol Cell Biol. 1983 Oct;3(10):1834–1845. doi: 10.1128/mcb.3.10.1834. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Goodwin G. H. Identification of three sequence-specific DNA-binding proteins which interact with the Rous sarcoma virus enhancer and upstream promoter elements. J Virol. 1988 Jun;62(6):2186–2190. doi: 10.1128/jvi.62.6.2186-2190.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. Greuel B. T., Sealy L., Majors J. E. Transcriptional activity of the Rous sarcoma virus long terminal repeat correlates with binding of a factor to an upstream CCAAT box in vitro. Virology. 1990 Jul;177(1):33–43. doi: 10.1016/0042-6822(90)90457-3. [DOI] [PubMed] [Google Scholar]
  16. Grueneberg D. A., Natesan S., Alexandre C., Gilman M. Z. Human and Drosophila homeodomain proteins that enhance the DNA-binding activity of serum response factor. Science. 1992 Aug 21;257(5073):1089–1095. doi: 10.1126/science.257.5073.1089. [DOI] [PubMed] [Google Scholar]
  17. Hayward W. S., Neel B. G., Astrin S. M. Activation of a cellular onc gene by promoter insertion in ALV-induced lymphoid leukosis. Nature. 1981 Apr 9;290(5806):475–480. doi: 10.1038/290475a0. [DOI] [PubMed] [Google Scholar]
  18. Hishinuma F., DeBona P. J., Astrin S., Skalka A. M. Nucleotide sequence of acceptor site and termini of integrated avian endogenous provirus ev1: integration creates a 6 bp repeat of host DNA. Cell. 1981 Jan;23(1):155–164. doi: 10.1016/0092-8674(81)90280-4. [DOI] [PubMed] [Google Scholar]
  19. Hughes S. H. Sequence of the long terminal repeat and adjacent segments of the endogenous avian virus Rous-associated virus 0. J Virol. 1982 Jul;43(1):191–200. doi: 10.1128/jvi.43.1.191-200.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Hughes S. H., Toyoshima K., Bishop J. M., Varmus H. E. Organization of the endogenous proviruses of chickens: implications for origin and expression. Virology. 1981 Jan 15;108(1):189–207. doi: 10.1016/0042-6822(81)90538-9. [DOI] [PubMed] [Google Scholar]
  21. Laimins L. A., Tsichlis P., Khoury G. Multiple enhancer domains in the 3' terminus of the Prague strain of Rous sarcoma virus. Nucleic Acids Res. 1984 Aug 24;12(16):6427–6442. doi: 10.1093/nar/12.16.6427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Linial M., Groudine M. Transcription of three c-myc exons is enhanced in chicken bursal lymphoma cell lines. Proc Natl Acad Sci U S A. 1985 Jan;82(1):53–57. doi: 10.1073/pnas.82.1.53. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Luciw P. A., Bishop J. M., Varmus H. E., Capecchi M. R. Location and function of retroviral and SV40 sequences that enhance biochemical transformation after microinjection of DNA. Cell. 1983 Jul;33(3):705–716. doi: 10.1016/0092-8674(83)90013-2. [DOI] [PubMed] [Google Scholar]
  24. Mariash C. N., Seelig S., Oppenheimer J. H. A rapid, inexpensive, quantitative technique for the analysis of two-dimensional electrophoretograms. Anal Biochem. 1982 Apr;121(2):388–394. doi: 10.1016/0003-2697(82)90498-5. [DOI] [PubMed] [Google Scholar]
  25. Mitsialis S. A., Manley J. L., Guntaka R. V. Localization of active promoters for eucaryotic RNA polymerase II in the long terminal repeat of avian sarcoma virus DNA. Mol Cell Biol. 1983 May;3(5):811–818. doi: 10.1128/mcb.3.5.811. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Mohun T. J., Chambers A. E., Towers N., Taylor M. V. Expression of genes encoding the transcription factor SRF during early development of Xenopus laevis: identification of a CArG box-binding activity as SRF. EMBO J. 1991 Apr;10(4):933–940. doi: 10.1002/j.1460-2075.1991.tb08027.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Moscovici C., Moscovici M. G., Jimenez H., Lai M. M., Hayman M. J., Vogt P. K. Continuous tissue culture cell lines derived from chemically induced tumors of Japanese quail. Cell. 1977 May;11(1):95–103. doi: 10.1016/0092-8674(77)90320-8. [DOI] [PubMed] [Google Scholar]
  28. Norton P. A., Coffin J. M. Characterization of Rous sarcoma virus sequences essential for viral gene expression. J Virol. 1987 Apr;61(4):1171–1179. doi: 10.1128/jvi.61.4.1171-1179.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Ozer J., Faber M., Chalkley R., Sealy L. Isolation and characterization of a cDNA clone for the CCAAT transcription factor EFIA reveals a novel structural motif. J Biol Chem. 1990 Dec 25;265(36):22143–22152. [PubMed] [Google Scholar]
  30. Payne G. S., Bishop J. M., Varmus H. E. Multiple arrangements of viral DNA and an activated host oncogene in bursal lymphomas. Nature. 1982 Jan 21;295(5846):209–214. doi: 10.1038/295209a0. [DOI] [PubMed] [Google Scholar]
  31. Robinson H. L. Inheritance and expression of chicken genes that are related to avian leukosis sarcoma virus genes. Curr Top Microbiol Immunol. 1978;83:1–36. doi: 10.1007/978-3-642-67087-9_1. [DOI] [PubMed] [Google Scholar]
  32. Ruddell A., Linial M. L., Groudine M. Tissue-specific lability and expression of avian leukosis virus long terminal repeat enhancer-binding proteins. Mol Cell Biol. 1989 Dec;9(12):5660–5668. doi: 10.1128/mcb.9.12.5660. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Ruddell A., Linial M., Schubach W., Groudine M. Lability of leukosis virus enhancer-binding proteins in avian hematopoeitic cells. J Virol. 1988 Aug;62(8):2728–2735. doi: 10.1128/jvi.62.8.2728-2735.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Ryan W. A., Jr, Franza B. R., Jr, Gilman M. Z. Two distinct cellular phosphoproteins bind to the c-fos serum response element. EMBO J. 1989 Jun;8(6):1785–1792. doi: 10.1002/j.1460-2075.1989.tb03572.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Ryden T. A., Beemon K. Avian retroviral long terminal repeats bind CCAAT/enhancer-binding protein. Mol Cell Biol. 1989 Mar;9(3):1155–1164. doi: 10.1128/mcb.9.3.1155. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Scholl D. R., Kahn S., Malavarca R., Astrin S., Skalka A. M. Nucleotide sequence of the long terminal repeat and flanking cellular sequences of avian endogenous retrovirus ev-2: variation in Rous-associated virus-0 expression cannot be explained by differences in primary sequence. J Virol. 1983 Feb;45(2):868–871. doi: 10.1128/jvi.45.2.868-871.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Schwartz D. E., Tizard R., Gilbert W. Nucleotide sequence of Rous sarcoma virus. Cell. 1983 Mar;32(3):853–869. doi: 10.1016/0092-8674(83)90071-5. [DOI] [PubMed] [Google Scholar]
  38. Sealey L., Chalkley R. At least two nuclear proteins bind specifically to the Rous sarcoma virus long terminal repeat enhancer. Mol Cell Biol. 1987 Feb;7(2):787–798. doi: 10.1128/mcb.7.2.787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Taylor M. V. A family of muscle gene promoter element (CArG) binding activities in Xenopus embryos: CArG/SRE discrimination and distribution during myogenesis. Nucleic Acids Res. 1991 May 25;19(10):2669–2675. doi: 10.1093/nar/19.10.2669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Treisman R. The SRE: a growth factor responsive transcriptional regulator. Semin Cancer Biol. 1990 Feb;1(1):47–58. [PubMed] [Google Scholar]
  41. Walsh K. Cross-binding of factors to functionally different promoter elements in c-fos and skeletal actin genes. Mol Cell Biol. 1989 May;9(5):2191–2201. doi: 10.1128/mcb.9.5.2191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Weber F., Schaffner W. Enhancer activity correlates with the oncogenic potential of avian retroviruses. EMBO J. 1985 Apr;4(4):949–956. doi: 10.1002/j.1460-2075.1985.tb03723.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Yamamoto T., de Crombrugghe B., Pastan I. Identification of a functional promoter in the long terminal repeat of Rous sarcoma virus. Cell. 1980 Dec;22(3):787–797. doi: 10.1016/0092-8674(80)90555-3. [DOI] [PubMed] [Google Scholar]
  44. Zachow K. R., Conklin K. F. CArG, CCAAT, and CCAAT-like protein binding sites in avian retrovirus long terminal repeat enhancers. J Virol. 1992 Apr;66(4):1959–1970. doi: 10.1128/jvi.66.4.1959-1970.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES