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Retrovirus-induced de novo methylation of flanking host sequences correlates with gene inactivity

Abstract

The pattern of DNA methylation changes during development of eukaryotes, and hypomethylation frequently correlates with gene expression (for reviews see refs 1–4). A causal relationship between hypermethylation and gene inactivity has been established for retroviral genomes which are methylated de novo when inserted into the germ line of mice (ref. 5; for review, see ref. 6). The mutual interaction of the provirus with the host genome can influence virus expression7 and can result in inactivation of the host gene by insertional mutagenesis8. We report here that the insertion of a provirus can change the methylation pattern of the host DNA. Sequences flanking the provirus become methylated de novo within 1 kilobase (kb) of the integration site. In Mov-13 mice, which carry a lethal mutation of the α 1(I) collagen gene9,10, de novo methylation of host DNA is associated with a change in chromatin conformation11. This suggests that virus-induced DNA methylation can alter DNA–protein interactions and thereby interfere with correct gene activation during embryonic development.

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References

  1. Cooper, D. N. Hum. Genet. 64, 315–333 (1983).

    Article  CAS  Google Scholar 

  2. Dörfler, W. A. Rev. Biochem. 52, 93–124 (1983).

    Article  Google Scholar 

  3. Jaenisch, R. & Jähner, D. Biochim. biophys. Acta 782, 1–9 (1984).

    Article  CAS  Google Scholar 

  4. Bird, A. P. Nature 307, 503–504 (1984).

    Article  ADS  CAS  Google Scholar 

  5. Jähner, D. et al. Nature 298, 623–628 (1982).

    Article  ADS  Google Scholar 

  6. Jähner, D. & Jaenisch, R. in DNA Methylation (eds Razin, A., Cedar, H. & Riggs, A.) 189–219 (Springer, New York, 1984).

    Book  Google Scholar 

  7. Jaenisch, R. et al. Cell 24, 519–529 (1981).

    Article  CAS  Google Scholar 

  8. Jaenisch, R. et al. Cell 32, 209–216 (1983).

    Article  CAS  Google Scholar 

  9. Schnieke, A., Harbers, K. & Jaenisch, R. Nature 304, 315–319 (1983).

    Article  ADS  CAS  Google Scholar 

  10. Harbers, K., Kuehn, M., Delius, H. & Jaenisch, R. Proc. natn. Acad. Sci. U.S.A 81, 1504–1508 (1984).

    Article  ADS  CAS  Google Scholar 

  11. Breindl, M., Harbers, K. & Jaenisch, R. Cell 38, 9–16 (1984).

    Article  CAS  Google Scholar 

  12. Chapman, V., Forrester, L., Sanford, J., Hastie, N. & Rossant, J. Nature 307, 284–286 (1984).

    Article  ADS  CAS  Google Scholar 

  13. Ponzetto-Zimmermann, C. & Wolgemuth, D. J. Nucleic Acids Res. 12, 2807–2822 (1984).

    Article  Google Scholar 

  14. Jähner, D. & Jaenisch, R. Molec. cell. Biol. (in the press).

  15. Stuhlmann, H., Jähner, D. & Jaenisch, R. Cell 26, 221–232 (1981).

    Article  CAS  Google Scholar 

  16. Harbers, K., Schnieke, A., Stuhlmann, H., Jähner, D. & Jaenisch, R. Proc. natn. Acad. Sci. U.S.A. 78, 7609–7613 (1981).

    Article  ADS  CAS  Google Scholar 

  17. Hoffmann, J. W. et al. J. Virol. 44, 144–157 (1982).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Stewart, C. L., Stuhlmann, H., Jähner, D. & Jaenisch, R. Proc. natn. Acad. Sci. U.S.A. 79, 4098–4102 (1982).

    Article  ADS  CAS  Google Scholar 

  19. Gautsch, J. W. & Wilson, M. C. Nature 301, 32–37 (1983).

    Article  ADS  CAS  Google Scholar 

  20. Niwa, O., Yokota, Y., Ishida, H. & Sugahara, T. Cell 32, 1105–1113 (1983).

    Article  CAS  Google Scholar 

  21. Palmiter, R. D., Chen, H. Y. & Brinster, R. L. Cell 29, 701–710 (1982).

    Article  CAS  Google Scholar 

  22. Lacy, E., Roberts, S., Evans, E. P., Burtenshaw, D. & Costantini, F. D. Cell 34, 343–358 (1983).

    Article  CAS  Google Scholar 

  23. Brinster, R. L. et al. Cell 37, 367–379 (1984).

    Article  CAS  Google Scholar 

  24. Stewart, T. A., Pattengale, P. K. & Leder, P. Cell 38, 627–637 (1984).

    Article  CAS  Google Scholar 

  25. Maniatis, T., Fritsch, E. F. & Sambrook, J. in Molecular Cloning (Cold Spring Harbor Laboratory, New York, 1982).

    Google Scholar 

  26. Chumakov, I., Stuhlmann, H., Harbers, K. & Jaenisch, R. J. Virol. 42, 1088–1098 (1982).

    CAS  PubMed  PubMed Central  Google Scholar 

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Jähner, D., Jaenisch, R. Retrovirus-induced de novo methylation of flanking host sequences correlates with gene inactivity. Nature 315, 594–597 (1985). https://doi.org/10.1038/315594a0

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