Abstract
Elements within the enhancer of T-lymphomagenic SL3-3 virus were examined for their contributions to transcriptional activity in T lymphocytes and non-T cells. A region containing two sequences homologous to the enhancer core consensus sequence and a sequence homologous to the binding site for factor LVb was found to have the largest effect on activity. Evidence was obtained that suggests that the activity of this region was greater in T lymphocytes than in non-T cells and that multiple elements within it were necessary for activity. A second region, containing sequences homologous to the binding site of factor NF-I and the glucocorticoid response element, had about a twofold effect on transcription in both T lymphocytes and non-T cell lines. The twofold effect was seen whether the region containing the cores and LVb site was present or not. These results indicate that the most important region for the specificity of SL3-3 enhancer activity and, presumably, for viral leukemogenicity comprises the core elements and the LVb site. DNA-protein-binding studies demonstrated that one cellular factor, S/A-CBF, bound to both core elements, while a second cellular factor, S-CBF, bound to only one of them. In combination with earlier studies, this indicates that cells contain multiple factors that bind to the critical region.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Arnott S., Chandrasekaran R., Puigjaner L. C., Walker J. K., Hall I. H., Birdsall D. L., Ratliff R. L. Wrinkled DNA. Nucleic Acids Res. 1983 Mar 11;11(5):1457–1474. doi: 10.1093/nar/11.5.1457. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Bösze Z., Thiesen H. J., Charnay P. A transcriptional enhancer with specificity for erythroid cells is located in the long terminal repeat of the Friend murine leukemia virus. EMBO J. 1986 Jul;5(7):1615–1623. doi: 10.1002/j.1460-2075.1986.tb04404.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Celander D., Hsu B. L., Haseltine W. A. Regulatory elements within the murine leukemia virus enhancer regions mediate glucocorticoid responsiveness. J Virol. 1988 Apr;62(4):1314–1322. doi: 10.1128/jvi.62.4.1314-1322.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chatis P. A., Holland C. A., Hartley J. W., Rowe W. P., Hopkins N. Role for the 3' end of the genome in determining disease specificity of Friend and Moloney murine leukemia viruses. Proc Natl Acad Sci U S A. 1983 Jul;80(14):4408–4411. doi: 10.1073/pnas.80.14.4408. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chatis P. A., Holland C. A., Silver J. E., Frederickson T. N., Hopkins N., Hartley J. W. A 3' end fragment encompassing the transcriptional enhancers of nondefective Friend virus confers erythroleukemogenicity on Moloney leukemia virus. J Virol. 1984 Oct;52(1):248–254. doi: 10.1128/jvi.52.1.248-254.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- DeFranco D., Yamamoto K. R. Two different factors act separately or together to specify functionally distinct activities at a single transcriptional enhancer. Mol Cell Biol. 1986 Apr;6(4):993–1001. doi: 10.1128/mcb.6.4.993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DesGroseillers L., Jolicoeur P. The tandem direct repeats within the long terminal repeat of murine leukemia viruses are the primary determinant of their leukemogenic potential. J Virol. 1984 Dec;52(3):945–952. doi: 10.1128/jvi.52.3.945-952.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Fromental C., Kanno M., Nomiyama H., Chambon P. Cooperativity and hierarchical levels of functional organization in the SV40 enhancer. Cell. 1988 Sep 23;54(7):943–953. doi: 10.1016/0092-8674(88)90109-2. [DOI] [PubMed] [Google Scholar]
- Gillis S., Smith K. A. Long term culture of tumour-specific cytotoxic T cells. Nature. 1977 Jul 14;268(5616):154–156. doi: 10.1038/268154a0. [DOI] [PubMed] [Google Scholar]
- Golemis E., Li Y., Fredrickson T. N., Hartley J. W., Hopkins N. Distinct segments within the enhancer region collaborate to specify the type of leukemia induced by nondefective Friend and Moloney viruses. J Virol. 1989 Jan;63(1):328–337. doi: 10.1128/jvi.63.1.328-337.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- Halpern M. S., Coffman R. L. Polymer formation and J chain synthesis in mouse plasmacytomas. J Immunol. 1972 Oct;109(4):674–680. [PubMed] [Google Scholar]
- Harris A. W., Bankhurst A. D., Mason S., Warner N. L. Differentiated functions expressed by cultured mouse lymphoma cells. II. Theta antigen, surface immunoglobulin and a receptor for antibody on cells of a thymoma cell line. J Immunol. 1973 Feb;110(2):431–438. [PubMed] [Google Scholar]
- Hays E. F., Margaretten N., Swanson S. K. Spontaneous leukemia viruses: lymphomagenic ecotropic viruses of AKR mice. J Natl Cancer Inst. 1982 Nov;69(5):1077–1082. [PubMed] [Google Scholar]
- 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]
- Ishimoto A., Takimoto M., Adachi A., Kakuyama M., Kato S., Kakimi K., Fukuoka K., Ogiu T., Matsuyama M. Sequences responsible for erythroid and lymphoid leukemia in the long terminal repeats of Friend-mink cell focus-forming and Moloney murine leukemia viruses. J Virol. 1987 Jun;61(6):1861–1866. doi: 10.1128/jvi.61.6.1861-1866.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jainchill J. L., Aaronson S. A., Todaro G. J. Murine sarcoma and leukemia viruses: assay using clonal lines of contact-inhibited mouse cells. J Virol. 1969 Nov;4(5):549–553. doi: 10.1128/jvi.4.5.549-553.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Li Y., Golemis E., Hartley J. W., Hopkins N. Disease specificity of nondefective Friend and Moloney murine leukemia viruses is controlled by a small number of nucleotides. J Virol. 1987 Mar;61(3):693–700. doi: 10.1128/jvi.61.3.693-700.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Manley N. R., O'Connell M. A., Sharp P. A., Hopkins N. Nuclear factors that bind to the enhancer region of nondefective Friend murine leukemia virus. J Virol. 1989 Oct;63(10):4210–4223. doi: 10.1128/jvi.63.10.4210-4223.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Maxam A. M., Gilbert W. A new method for sequencing DNA. Proc Natl Acad Sci U S A. 1977 Feb;74(2):560–564. doi: 10.1073/pnas.74.2.560. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McGrath M. S., Pillemer E., Kooistra D., Weissman I. L. The role of MuLV receptors on T-lymphoma cells in lymphoma cell proliferation. Contemp Top Immunobiol. 1980;11:157–184. doi: 10.1007/978-1-4684-3701-0_5. [DOI] [PubMed] [Google Scholar]
- Nilsson P., Hallberg B., Thornell A., Grundström T. Mutant analysis of protein interactions with a nuclear factor I binding site in the SL3-3 virus enhancer. Nucleic Acids Res. 1989 Jun 12;17(11):4061–4075. doi: 10.1093/nar/17.11.4061. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ondek B., Gloss L., Herr W. The SV40 enhancer contains two distinct levels of organization. Nature. 1988 May 5;333(6168):40–45. doi: 10.1038/333040a0. [DOI] [PubMed] [Google Scholar]
- Ralph P. Retention of lymphocyte characteristics by myelomas and theta + -lymphomas: sensitivity to cortisol and phytohemagglutinin. J Immunol. 1973 Jun;110(6):1470–1475. [PubMed] [Google Scholar]
- 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]
- 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]
- Thiesen H. J., Bösze Z., Henry L., Charnay P. A DNA element responsible for the different tissue specificities of Friend and Moloney retroviral enhancers. J Virol. 1988 Feb;62(2):614–618. doi: 10.1128/jvi.62.2.614-618.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- Vogt M., Haggblom C., Swift S., Haas M. Envelope gene and long terminal repeat determine the different biological properties of Rauscher, Friend, and Moloney mink cell focus-inducing viruses. J Virol. 1985 Jul;55(1):184–192. doi: 10.1128/jvi.55.1.184-192.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- Yuen P. H., Szurek P. F. The reduced virulence of the thymotropic Moloney murine leukemia virus derivative MoMuLV-TB is mapped to 11 mutations within the U3 region of the long terminal repeat. J Virol. 1989 Feb;63(2):471–480. doi: 10.1128/jvi.63.2.471-480.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]