Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Effect of ageing on reactivation of the human X-linked HPRT locus

Nature volume 335, pages 93–96 (1988)Cite this article

Abstract

In mammals, X-chromosome dosage compensation is achieved by inactivating one X chromosome in female cells1. To test the hypothesis2 that genes on the silent X chromosome reactivate as a consequence of ageing, we examined the X-linked hypoxanthine phosphoribosyltransferase (HPRT) locus in 41 women who are heterozygous for mutations at this locus, leading to severe deficiency of the enzyme (Lesch-Nyhan syndrome3). We find that heterozygotes who are more than 10 yr old have an excess of HPRT+ skin fibroblast clones (59% rather than the 50% expected as a consequence of random X inactivation) but this excess does not increase with age. Further studies of eight of these heterozygotes show that the silent locus does not detectably reactivate spontaneously in culture, but only in response to treatment with 5-aza-2-deoxycytidine, a potent inhibitor of methylation. There is no age difference in the frequency of this reactivation as assayed by HATr clones, and a more sensitive autoradiographic assay shows only a twofold difference between young and old heterozy-gotes. Thus, age-related reactivation is not a feature of all X-linked loci, and may have species, tissue and locus-specific determinants.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Lyon, M. F. Biol. Rev. 47, 1–35 (1972).

    Article  CAS  Google Scholar 

  2. Wareham, K. A., Lyon, M. F., Glenister, P. H. & Williams, E. D. Nature 327, 725–727 (1987).

    Article  CAS  ADS  Google Scholar 

  3. Lesch, M. & Nyhan, W. L. Am. J. Med. 36, 561–570 (1964).

    Article  CAS  Google Scholar 

  4. Cattanach, B. M. Genet. Res. 23, 291–306 (1974).

    Article  CAS  Google Scholar 

  5. Holliday, R. & Tarrant, G. M. Nature 238, 26–30 (1972).

    Article  CAS  ADS  Google Scholar 

  6. Holliday, R. Expl Cell Res. 166, 543–552 (1986).

    Article  CAS  Google Scholar 

  7. Holliday, R. Nature 327, 661–662 (1987).

    Article  CAS  ADS  Google Scholar 

  8. Harris, M. Cell 29, 483–492 (1982).

    Article  CAS  Google Scholar 

  9. Migeon, B. R., Der Kaloustian, V. M., Nyhan, W. L., Young, W. J. & Childs, B. Science 160, 425–427 (1968).

    Article  CAS  ADS  Google Scholar 

  10. Migeon, B. R. Biochem. Genet. 4, 377–384 (1970).

    Article  CAS  Google Scholar 

  11. Migcon, B. R. Am. J. hum. Genet. 23, 199–210 (1971).

    Google Scholar 

  12. Trainor, K. J. et al. in Mechanisms of Ageing and Development 27, 83–86 (1984).

    Article  CAS  Google Scholar 

  13. Nyhan, W. L., Bakay, B., Connor, J. D., Marks, J. F. & Keele, D. K. Proc. natn. Acad. Sci. U.S.A. 65, 214–218 (1970).

    Article  CAS  ADS  Google Scholar 

  14. Dancis, J. et al. Life Sci. 7, 587–591 (1968).

    Article  CAS  Google Scholar 

  15. Albertini, R. J. & DeMars, R. Biochem. Genet. 11, 397–411 (1974).

    Article  CAS  Google Scholar 

  16. Mohandas, T., Sparkes, R. S. & Shapiro, L. J. Science 211, 393–396 (1981).

    Article  CAS  ADS  Google Scholar 

  17. Beggs, A., Axelman, J. & Migeon, B. R. Somatic Cell Genet. 12, 585–594 (1986).

    Article  CAS  Google Scholar 

  18. Kaslow, D. C. & Migeon, B. R. Proc. natn. Acad. Sci. U.S.A. 84, 6210–6214 (1987).

    Article  CAS  ADS  Google Scholar 

  19. Wolf, S. F., Jolly, D. J., Lunnen, K. D., Friedmann, T. & Migeon, B. R. Proc. natn. Acad. Sci. U.S.A. 81, 2806–2810 (1984).

    Article  CAS  ADS  Google Scholar 

  20. Yen, P. H., Patel, P., Chinault, A. C., Mohandas, T. & Shapiro, L. J. Proc. natn. Acad. Sci. U.S.A. 81, 1759–1763 (1984).

    Article  CAS  ADS  Google Scholar 

  21. Migeon, B. R. Nature 239, 87–89 (1972).

    Article  CAS  ADS  Google Scholar 

  22. Wolf, S. F. & Migeon, B. R. Nature 295, 667–671 (1982).

    Article  CAS  ADS  Google Scholar 

  23. Wolf, S. F. et al. Nucleic Acids Res. 12, 9333–9348 (1984).

    Article  CAS  Google Scholar 

  24. Riggs, A. D., Singer-Sam, J. & Keith, D. H. in Biology and Biochemistry of DNA Methylation (eds Cantoni, G. L. & Razin, A.) 211–222 (Liss, New York, 1985).

    Google Scholar 

  25. Bird, A. P. Nature 321, 209–213 (1986).

    Article  CAS  ADS  Google Scholar 

  26. Ruta Cullen, C., Hubberman, P., Kaslow, D. C. & Migeon, B. R. EMBO J. 9, 2223–2229 (1986).

    Article  Google Scholar 

  27. Hannibal, M. C., Cullen, C. R., Kaslow, D. C., Davies, K. E. & Migeon, B. R. Am. J. hum. Genet. 39, A201 (1986).

    Google Scholar 

  28. Mullins, L. J., Veres, G., Caskey, C. T. & Chapman, V. Molec. cell. Biol. 7, 3916–3922 (1987).

    Article  CAS  Google Scholar 

  29. Wilson, V. L., Smith, R. A., Mas, S. & Cutler, R. G. J. biol. Chem. 262, 9948–9951 (1987).

    CAS  PubMed  Google Scholar 

  30. Fairweather, D. S., Fox, M. & Margison, G. P. Expl Cell Res. 168, 153–159 (1987).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205, USA

    Barbara R. Migeon, Joyce Axelman & Alan H. Beggs

Authors
  1. Barbara R. Migeon
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joyce Axelman
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alan H. Beggs
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Migeon, B., Axelman, J. & Beggs, A. Effect of ageing on reactivation of the human X-linked HPRT locus. Nature 335, 93–96 (1988). https://doi.org/10.1038/335093a0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/335093a0

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing