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. 1982 Jan 22;10(2):577–592. doi: 10.1093/nar/10.2.577

Moloney murine leukemia virus-induced tumors: recombinant proviruses in active chromatin regions.

H van der Putten, W Quint, I M Verma, A Berns
PMCID: PMC326159  PMID: 6278422

Abstract

The DNase I sensitivity of chromosomal DNA regions carrying integrated proviral genomes of Moloney (M-MuLV) and AKR Murine Leukemia Virus (AKR-MuLV), and the cellular homologue of the mos-gene (c-mos) of Moloney Sarcoma Virus (MSV) were studied in tumor tissues of leukemic mice. The genetically transmitted sequences of M-MuLV, AKR-MuLV, and the c-mos gene are all in DNase I resistant chromatin conformations in M-MuLV-induced tumors. Each M-MuLV-induced tumor contained at least one somatically acquired integrated recombinant MuLV genome that displayed two main characteristic features of active chromatin: a) a configuration hypersensitive to DNase I, and b) extensive hypomethylation. DNase I hypersensitive sites were mapped at the junction of cellular sequences and the 5'-viral large terminal repeat (LTR). Expression of a recombinant MuLV seems therefore to be a necessary feature to maintain the transformed state.

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Selected References

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  1. Berns A., Jaenisch R. Increase of AKR-specific sequences in tumor tissues of leukemic AKR mice. Proc Natl Acad Sci U S A. 1976 Jul;73(7):2448–2452. doi: 10.1073/pnas.73.7.2448. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Breindl M., Bacheler L., Fan H., Jaenisch R. Chromatin conformation of integrated Moloney leukemia virus DNA sequences in tissues of BALB/Mo mice and in virus-infected cell lines. J Virol. 1980 May;34(2):373–382. doi: 10.1128/jvi.34.2.373-382.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Breindl M., Doehmer J., Willecke K., Dausman J., Jaenisch R. Germ line integration of Moloney leukemia virus: identification of the chromosomal integration site. Proc Natl Acad Sci U S A. 1979 Apr;76(4):1938–1942. doi: 10.1073/pnas.76.4.1938. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Canaani E., Aaronson S. A. Restriction enzyme analysis of mouse cellular type C viral DNA: emergence of new viral sequences in spontaneous AKR/J lymphomas. Proc Natl Acad Sci U S A. 1979 Apr;76(4):1677–1681. doi: 10.1073/pnas.76.4.1677. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. Jaenisch R., Fan H., Croker B. Infection of preimplantation mouse embryos and of newborn mice with leukemia virus: tissue distribution of viral DNA and RNA and leukemogenesis in the adult animal. Proc Natl Acad Sci U S A. 1975 Oct;72(10):4008–4012. doi: 10.1073/pnas.72.10.4008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Jaenisch R. Moloney leukemia virus gene expression and gene amplification in preleukemic and leukemic BALB/Mo mice. Virology. 1979 Feb;93(1):80–90. doi: 10.1016/0042-6822(79)90277-0. [DOI] [PubMed] [Google Scholar]
  8. Jolicoeur P., Rosenberg N., Cotellessa A., Baltimore D. Leukemogenicity of clonal isolates of murine leukemia viruses. J Natl Cancer Inst. 1978 Jun;60(6):1473–1476. doi: 10.1093/jnci/60.6.1473. [DOI] [PubMed] [Google Scholar]
  9. Jolicoeur P. The Fv-1 gene of the mouse and its control of murine leukemia virus replication. Curr Top Microbiol Immunol. 1979;86:67–122. doi: 10.1007/978-3-642-67341-2_3. [DOI] [PubMed] [Google Scholar]
  10. Jähner D., Stuhlmann H., Jaenisch R. Conformation of free and of integrated Moloney leukemia virus proviral DNA in preleukemic and leukemic BALB/Mo mice. Virology. 1980 Feb;101(1):111–123. doi: 10.1016/0042-6822(80)90488-2. [DOI] [PubMed] [Google Scholar]
  11. Keene M. A., Corces V., Lowenhaupt K., Elgin S. C. DNase I hypersensitive sites in Drosophila chromatin occur at the 5' ends of regions of transcription. Proc Natl Acad Sci U S A. 1981 Jan;78(1):143–146. doi: 10.1073/pnas.78.1.143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Mathis D., Oudet P., Chambon P. Structure of transcribing chromatin. Prog Nucleic Acid Res Mol Biol. 1980;24:1–55. doi: 10.1016/s0079-6603(08)60670-4. [DOI] [PubMed] [Google Scholar]
  13. Neel B. G., Hayward W. S., Robinson H. L., Fang J., Astrin S. M. Avian leukosis virus-induced tumors have common proviral integration sites and synthesize discrete new RNAs: oncogenesis by promoter insertion. Cell. 1981 Feb;23(2):323–334. doi: 10.1016/0092-8674(81)90128-8. [DOI] [PubMed] [Google Scholar]
  14. Nobis P., Jaenisch R. Passive immunotherapy prevents expression of endogenous Moloney virus and amplification of proviral DNA in BALB/Mo mice. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3677–3681. doi: 10.1073/pnas.77.6.3677. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Payne G. S., Courtneidge S. A., Crittenden L. B., Fadly A. M., Bishop J. M., Varmus H. E. Analysis of avian leukosis virus DNA and RNA in bursal tumours: viral gene expression is not required for maintenance of the tumor state. Cell. 1981 Feb;23(2):311–322. doi: 10.1016/0092-8674(81)90127-6. [DOI] [PubMed] [Google Scholar]
  16. Quint W., Quax W., van der Putten H., Berns A. Characterization of AKR murine leukemia virus sequences in AKR mouse substrains and structure of integrated recombinant genomes in tumor tissues. J Virol. 1981 Jul;39(1):1–10. doi: 10.1128/jvi.39.1.1-10.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Reddy E. P., Dunn C. Y., Aaronson S. A. Different lymphoid cell targets by transformation by replication-competent Moloney and Rauscher mouse leukemia viruses. Cell. 1980 Mar;19(3):663–669. doi: 10.1016/s0092-8674(80)80043-2. [DOI] [PubMed] [Google Scholar]
  18. Samal B., Worcel A., Louis C., Schedl P. Chromatin structure of the histone genes of D. melanogaster. Cell. 1981 Feb;23(2):401–409. doi: 10.1016/0092-8674(81)90135-5. [DOI] [PubMed] [Google Scholar]
  19. Stalder J., Groudine M., Dodgson J. B., Engel J. D., Weintraub H. Hb switching in chickens. Cell. 1980 Apr;19(4):973–980. doi: 10.1016/0092-8674(80)90088-4. [DOI] [PubMed] [Google Scholar]
  20. Stalder J., Larsen A., Engel J. D., Dolan M., Groudine M., Weintraub H. Tissue-specific DNA cleavages in the globin chromatin domain introduced by DNAase I. Cell. 1980 Jun;20(2):451–460. doi: 10.1016/0092-8674(80)90631-5. [DOI] [PubMed] [Google Scholar]
  21. Steffen D., Bird S., Rowe W. P., Weinberg R. A. Identification of DNA fragments carrying ecotropic proviruses of AKR mice. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4554–4558. doi: 10.1073/pnas.76.9.4554. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Steffen D., Weinberg R. A. The integrated genome of murine leukemia virus. Cell. 1978 Nov;15(3):1003–1010. doi: 10.1016/0092-8674(78)90284-2. [DOI] [PubMed] [Google Scholar]
  23. Weintraub H., Larsen A., Groudine M. Alpha-Globin-gene switching during the development of chicken embryos: expression and chromosome structure. Cell. 1981 May;24(2):333–344. doi: 10.1016/0092-8674(81)90323-8. [DOI] [PubMed] [Google Scholar]
  24. Weintraub H. Recognition of specific DNA sequences in eukaryotic chromosomes. Nucleic Acids Res. 1980 Oct 24;8(20):4745–4753. doi: 10.1093/nar/8.20.4745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Wu C. The 5' ends of Drosophila heat shock genes in chromatin are hypersensitive to DNase I. Nature. 1980 Aug 28;286(5776):854–860. doi: 10.1038/286854a0. [DOI] [PubMed] [Google Scholar]
  26. van der Putten H., Quint W., van Raaij J., Maandag E. R., Verma I. M., Berns A. M-MuLV-induced leukemogenesis: integration and structure of recombinant proviruses in tumors. Cell. 1981 Jun;24(3):729–739. doi: 10.1016/0092-8674(81)90099-4. [DOI] [PubMed] [Google Scholar]
  27. van der Putten H., Terwindt E., Berns A., Jaenisch R. The integration sites of endogenous and exogenous Moloney murine leukemia virus. Cell. 1979 Sep;18(1):109–116. doi: 10.1016/0092-8674(79)90359-3. [DOI] [PubMed] [Google Scholar]

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