Abstract
We used the electrophoretic mobility shift assay to identify the interactions of nuclear proteins with the long terminal repeat of leukemogenic, thymotropic BL/VL3 radiation leukemia virus (RadLV). In the promoter region, we identified a CCAAT box-binding protein (CBP) that has the same binding characteristics as the CCAAT box-binding protein that binds to the Moloney murine sarcoma virus promoter and most likely represents the CP1 factor. In the upstream enhancer region unique to BL/VL3, we detected several sequence-specific complexes, one with T-lymphocyte extracts but not with fibroblast extracts. This U3 region, UEB, may be important for the T-cell specificity of BL/VL3 RadLV. In the enhancer, which has been uniquely rearranged in this virus, we identified three specific protein-binding sites. Two of them showed characteristics of the LVb and core binding sites previously described for other murine retroviruses. But one binding site, identified as Rad-1, is unique to BL/VL3 RadLV and was found downstream, only 1 nucleotide from the core sequence. Rad-1 has a corelike motif on the minus strand, and the factor that binds to it could be competed by a BL/VL3 core-containing fragment. Moreover, the protein-DNA contacts involve the typical three core Gs separated by one T. These results suggest that Rad-1 binds a factor identical or similar to the core-binding factor. Our data suggest that the LVb, core, and Rad-1 motifs may be sufficient for this enhancer, most likely in association with other U3 long terminal repeat sequences, to promote a high rate of transcription of BL/VL3 RadLV in its specific target cells (thymocytes).
Full text
PDF






Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Becker P. B., Ruppert S., Schütz G. Genomic footprinting reveals cell type-specific DNA binding of ubiquitous factors. Cell. 1987 Nov 6;51(3):435–443. doi: 10.1016/0092-8674(87)90639-8. [DOI] [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]
- 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]
- Chodosh L. A., Baldwin A. S., Carthew R. W., Sharp P. A. Human CCAAT-binding proteins have heterologous subunits. Cell. 1988 Apr 8;53(1):11–24. doi: 10.1016/0092-8674(88)90483-7. [DOI] [PubMed] [Google Scholar]
- Cohen R. B., Sheffery M., Kim C. G. Partial purification of a nuclear protein that binds to the CCAAT box of the mouse alpha 1-globin gene. Mol Cell Biol. 1986 Mar;6(3):821–832. doi: 10.1128/mcb.6.3.821. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Declève A., Sato C., Lieberman M., Kaplan H. S. Selective thymic localization of murine leukemia virus-related antigens in C57BL-Ka mice after inoculation with radiation virus. Proc Natl Acad Sci U S A. 1974 Aug;71(8):3124–3128. doi: 10.1073/pnas.71.8.3124. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DesGroseillers L., Jolicoeur P. Mapping the viral sequences conferring leukemogenicity and disease specificity in Moloney and amphotropic murine leukemia viruses. J Virol. 1984 Nov;52(2):448–456. doi: 10.1128/jvi.52.2.448-456.1984. [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]
- DesGroseillers L., Rassart E., Jolicoeur P. Thymotropism of murine leukemia virus is conferred by its long terminal repeat. Proc Natl Acad Sci U S A. 1983 Jul;80(14):4203–4207. doi: 10.1073/pnas.80.14.4203. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DesGroseillers L., Rassart E., Robitaille Y., Jolicoeur P. Retrovirus-induced spongiform encephalopathy: the 3'-end long terminal repeat-containing viral sequences influence the incidence of the disease and the specificity of the neurological syndrome. Proc Natl Acad Sci U S A. 1985 Dec;82(24):8818–8822. doi: 10.1073/pnas.82.24.8818. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Dignam J. D., Lebovitz R. M., Roeder R. G. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983 Mar 11;11(5):1475–1489. doi: 10.1093/nar/11.5.1475. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dorn A., Bollekens J., Staub A., Benoist C., Mathis D. A multiplicity of CCAAT box-binding proteins. Cell. 1987 Sep 11;50(6):863–872. doi: 10.1016/0092-8674(87)90513-7. [DOI] [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]
- 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]
- Graves B. J., Johnson P. F., McKnight S. L. Homologous recognition of a promoter domain common to the MSV LTR and the HSV tk gene. Cell. 1986 Feb 28;44(4):565–576. doi: 10.1016/0092-8674(86)90266-7. [DOI] [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]
- Holland C. A., Thomas C. Y., Chattopadhyay S. K., Koehne C., O'Donnell P. V. Influence of enhancer sequences on thymotropism and leukemogenicity of mink cell focus-forming viruses. J Virol. 1989 Mar;63(3):1284–1292. doi: 10.1128/jvi.63.3.1284-1292.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Janowski M., Merregaert J., Boniver J., Maisin J. R. Proviral genome of radiation leukemia virus: molecular cloning of biologically active proviral DNA and nucleotide sequence of its long terminal repeat. J Virol. 1985 Jul;55(1):251–255. doi: 10.1128/jvi.55.1.251-255.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- Kaplan H. S. On the natural history of the murine leukemias: presidential address. Cancer Res. 1967 Aug;27(8):1325–1340. [PubMed] [Google Scholar]
- Khan A. S., Martin M. A. Endogenous murine leukemia proviral long terminal repeats contain a unique 190-base-pair insert. Proc Natl Acad Sci U S A. 1983 May;80(9):2699–2703. doi: 10.1073/pnas.80.9.2699. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kovesdi I., Reichel R., Nevins J. R. Identification of a cellular transcription factor involved in E1A trans-activation. Cell. 1986 Apr 25;45(2):219–228. doi: 10.1016/0092-8674(86)90386-7. [DOI] [PubMed] [Google Scholar]
- Landschulz W. H., Johnson P. F., Adashi E. Y., Graves B. J., McKnight S. L. Isolation of a recombinant copy of the gene encoding C/EBP. Genes Dev. 1988 Jul;2(7):786–800. doi: 10.1101/gad.2.7.786. [DOI] [PubMed] [Google Scholar]
- Lee W., Mitchell P., Tjian R. Purified transcription factor AP-1 interacts with TPA-inducible enhancer elements. Cell. 1987 Jun 19;49(6):741–752. doi: 10.1016/0092-8674(87)90612-x. [DOI] [PubMed] [Google Scholar]
- Lenardo M. J., Baltimore D. NF-kappa B: a pleiotropic mediator of inducible and tissue-specific gene control. Cell. 1989 Jul 28;58(2):227–229. doi: 10.1016/0092-8674(89)90833-7. [DOI] [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]
- Levinson B., Khoury G., Vande Woude G., Gruss P. Activation of SV40 genome by 72-base pair tandem repeats of Moloney sarcoma virus. Nature. 1982 Feb 18;295(5850):568–572. doi: 10.1038/295568a0. [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]
- Lieberman M., Declève A., Kaplan H. S. Rapid in vitro assay for thymotropic, leukemogenic murine C-type RNA viruses. Virology. 1978 Oct 15;90(2):274–278. doi: 10.1016/0042-6822(78)90311-2. [DOI] [PubMed] [Google Scholar]
- Lieberman M., Niwa O., Declève A., Kaplan H. S. Continuous propagation of radiation leukemia virus on a C57BL mouse-embryo fibroblast line, with attenuation of leukemogenic activity. Proc Natl Acad Sci U S A. 1973 Apr;70(4):1250–1253. doi: 10.1073/pnas.70.4.1250. [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]
- 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]
- 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. 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]
- 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]
- Mitchell P. J., Tjian R. Transcriptional regulation in mammalian cells by sequence-specific DNA binding proteins. Science. 1989 Jul 28;245(4916):371–378. doi: 10.1126/science.2667136. [DOI] [PubMed] [Google Scholar]
- Rassart E., Paquette Y., Jolicoeur P. Inability of Kaplan radiation leukemia virus to replicate on mouse fibroblasts is conferred by its long terminal repeat. J Virol. 1988 Oct;62(10):3840–3848. doi: 10.1128/jvi.62.10.3840-3848.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rassart E., Sankar-Mistry P., Lemay G., DesGroseillers L., Jolicoeur P. New class of leukemogenic ecotropic recombinant murine leukemia virus isolated from radiation-induced thymomas of C57BL/6 mice. J Virol. 1983 Feb;45(2):565–575. doi: 10.1128/jvi.45.2.565-575.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rassart E., Shang M., Boie Y., Jolicoeur P. Studies on emerging radiation leukemia virus variants in C57BL/Ka mice. J Virol. 1986 Apr;58(1):96–106. doi: 10.1128/jvi.58.1.96-106.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rosen C. A., Haseltine W. A., Lenz J., Ruprecht R., Cloyd M. W. Tissue selectivity of murine leukemia virus infection is determined by long terminal repeat sequences. J Virol. 1985 Sep;55(3):862–866. doi: 10.1128/jvi.55.3.862-866.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Scheidereit C., Heguy A., Roeder R. G. Identification and purification of a human lymphoid-specific octamer-binding protein (OTF-2) that activates transcription of an immunoglobulin promoter in vitro. Cell. 1987 Dec 4;51(5):783–793. doi: 10.1016/0092-8674(87)90101-2. [DOI] [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]
- Strauss F., Varshavsky A. A protein binds to a satellite DNA repeat at three specific sites that would be brought into mutual proximity by DNA folding in the nucleosome. Cell. 1984 Jul;37(3):889–901. doi: 10.1016/0092-8674(84)90424-0. [DOI] [PubMed] [Google Scholar]
- Struhl K. Naturally occurring poly(dA-dT) sequences are upstream promoter elements for constitutive transcription in yeast. Proc Natl Acad Sci U S A. 1985 Dec;82(24):8419–8423. doi: 10.1073/pnas.82.24.8419. [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]
- 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]
- 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]




