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.

  • Article
  • Published:

Methylation of the mouse Xist gene in sperm and eggs correlates with imprinted Xist expression and paternal X–inactivation

Nature Genetics volume 9, pages 316–320 (1995)Cite this article

Abstract

Preferential paternal X–inactivation in the extra–embryonic tissues of the female mouse embryo is correlated with imprinted expression of the paternal allele of the Xist gene in pre–implantation development. Here we examine 11 CpG sites in Xist to determine whether differential methylation might be the molecular basis for imprinting. We find that three sites in the promoter region are methylated in eggs but not in sperm and that this differential methylation is maintained to the blastocyst stage when the paternal X–inactivation occurs. This is the first example of a primary gametic methylation imprint governing differential expression of parental alleles in pre–implantation embryos.

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. Gene action in the X chromosome of the mouse (Mus musculus L.). Nature 190, 373 (1961).

    Article  Google Scholar 

  2. Grant, M., Zuccotti, M. & Monk, M. Methylation of CpG sites of two X-linked genes coincides with X-inactivation in the female mouse embryo but not in the germ line. Nature Genet. 2, 161–166 (1992).

    Article  CAS  PubMed  Google Scholar 

  3. Brown, C.J. et al. A gene from the region of the X-inactivation center is expressed exclusively from the inactive X chromosome. Nature 349, 38–44 (1991).

    Article  CAS  PubMed  Google Scholar 

  4. Brockdorff, N. et al. Conservation of position and exclusive expression of mouse Xist from the inactive X chromosome. Nature 351, 329–331 (1991).

    Article  CAS  PubMed  Google Scholar 

  5. Kay, G.F., Barton, S.C., Surani, M.A. & Rastan, S. Imprinting and X chromosome counting mechanisms determine Xist expression in early mouse development. Cell 77, 639–650 (1994).

    Article  CAS  PubMed  Google Scholar 

  6. Monk, M. & Harper, M. Sequential X-chromosome inactivation coupled with Cellular differentiation in early mouse embryos. Nature 281, 311–313 (1979).

    Article  CAS  PubMed  Google Scholar 

  7. Takagi, N. & Sasaki, M. Preferential expression of the paternally derived X chromosome in the extraembryonic membranes of the mouse. Nature 256, 640–642 (1975).

    Article  CAS  PubMed  Google Scholar 

  8. West, J.D., Frels, W.I., Chapman, V.M. & Papaioannou, V.E. Preferential expression of the maternally derived X chromosome in the mouse yolk sac. Cell 12, 873–882 (1977).

    Article  CAS  PubMed  Google Scholar 

  9. Harper, M.I., Fosten, M. & Monk, M. Preferential paternal X inactivation in extraembryonic tissues of early mouse embryos. J. Embryol. exp. Morph. 67, 127–135 (1982).

    CAS  PubMed  Google Scholar 

  10. Kay, G.F. et al. Expression of Xist during mouse development suggest a role in the initiation of X chromosome inactivation. Cell 72, 171–182 (1993).

    Article  CAS  PubMed  Google Scholar 

  11. Norris, D.P. et al. Evidence that random and imprinted expression is controlled by preemptive methylation. Cell 77, 41–51 (1994).

    Article  CAS  PubMed  Google Scholar 

  12. Singer-Sam, J. et al. DNA methylation in the 5′ region of the mouse Pgk-1 gene and a quantitative PCR assay for methylation. In UCLA Symposia on Molecular and Cellular Biology 128 (eds Clawson, G. et al.) (Alan R. Liss, New York, (1989).

    Google Scholar 

  13. Singer-Sam, J. et al. Use of an HpaII-polymerase chain reaction assay to study DNA methylation at the PgK-1 CpG island of mouse embryos at the time of X-chromosome inactivation. Molec. Cell. Biol 10, 4987–4989 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Monk, M., Boubelik, M. & Lehnert, S. Temporal and regional changes in DNA methylation in the embryonic, extraembryonic and germ Cell lineages during mouse embryo development. Development 99, 371–382 (1987).

    CAS  PubMed  Google Scholar 

  15. Razin, A. & Cedar, H. DNA methylation and genomic imprinting. Cell 77, 473–476 (1994).

    Article  CAS  PubMed  Google Scholar 

  16. Monk, M. Methylation and the X chromosome. BioEssays 4, 204–208 (1986).

    Article  CAS  PubMed  Google Scholar 

  17. Grant, S. & Chapman, V. Mechanisms of X-chromosome inactivation. M. A. Rev. Genet. 22, 199–233 (1988).

    Article  CAS  Google Scholar 

  18. Kafri, T. et al. Developmental pattern of gene-specific DNA methylation in the mouse embryo and germ line. Genes Dev. 6, 705–714 (1992).

    Article  CAS  PubMed  Google Scholar 

  19. McCarrey, J.R. & Dilworth, D.D. Expression of Xist in mouse germ Cells correlates with X-chromosome inactivation. Nature Genet. 2, 200–203 (1992).

    Article  CAS  PubMed  Google Scholar 

  20. Salido, E.D., Yen, P.H., Mohandas, T.K. & Shapiro, L.J. Expression of the X-inactivation-associated-gene Xist during spermatogenesis. Nature Genet. 2, 196–199 (1992).

    Article  CAS  PubMed  Google Scholar 

  21. Brandeis, M. et al. The ontogeny of allele-specific methylation associated with imprinted genes in the mouse. EMBO J. 12, 3669–3677 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Glenn, C.C., Porter, K.A., Jong, M.T.C., Nicholls, R.D. & Driscoll, D.J. Functional imprinting and epigenetic modification of the human SNRP gene. Hum. molec. Genet. 2, 2001–2005 (1993).

    Article  CAS  PubMed  Google Scholar 

  23. Sutcliffe, J.S. et al. Deletions of differentially methylated CpG island at the SNPP gene define a putative imprinting control region. Nature Genet. 8, 52–58 (1994).

    Article  CAS  PubMed  Google Scholar 

  24. Stoger, R. et al. Maternal-specific methylation of the imprinted mouse Igf2r locus identifies the expressed locus as carrying the imprinted signal. Cell 73, 61–71 (1993).

    Article  CAS  PubMed  Google Scholar 

  25. Bartoiomei, M.S., Webber, A.L., Brunkov, M.E. & Tilghman, S.M. Epigenetic mechanisms underlaying the imprinting of the mouse H19 gene. Genes Dev. 7, 1663–1673 (1993).

    Article  Google Scholar 

  26. Ferguson-Smith, A.C., Sasaki, H., Cattanach, B.M. & Surani, M.A. Parental-origin-speciflc epigenetic modification of the mouse H19 gene. Nature 362, 751–755 (1993).

    Article  CAS  PubMed  Google Scholar 

  27. Chaillet, J.R., Vogt, T.F., Beier, D.R. & Leder, P. (1991). Parental-specific methylation of an imprinted transgene is established during gametogenesis and progressively changes during embryogenesis. Cell 66, 77–83 (1991).

    Article  CAS  PubMed  Google Scholar 

  28. Monk, M. (ed.) Mammalian Development – practical Approach (IRL Press, Oxford, (1987).

    Google Scholar 

  29. Reik, W., Collick, A., Norris, M.L., Barton, S.C. & Surani, M.A., Genomic imprinting determines methylation of parental alleles in transgenic mice. Nature 328, 248–251 (1987).

    Article  CAS  PubMed  Google Scholar 

  30. Zuccotti, M., Grant, M. & Monk, M. Polymerase chain reaction for the detection of methylation of a specific CpG site in the G6pd gene of mouse embryos. Meth. Enzymol. 225, 557–567 (1993).

    Article  CAS  Google Scholar 

  31. Brockdorff, N. et al. The product of the mouse Xist gene is a 15 Kb Inactive X-specific transcript cointaining no conserved ORF and located in the nucleus. Cell 71, 515–526 (1992).

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Molecular Embryology Unit, Institute of Child Health, University of London, 30 Guilford Street, London, WC1N 1EH, UK

    Maurizio Zuccotti & Marilyn Monk

  2. Dipartimento Biologia Animale and Centra Studi per l'Istochimica del CNR, University of Pavia, Piazza Botta 10, Pavia, 27100, Italy

    Maurizio Zuccotti

Authors
  1. Maurizio Zuccotti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marilyn Monk
    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

Zuccotti, M., Monk, M. Methylation of the mouse Xist gene in sperm and eggs correlates with imprinted Xist expression and paternal X–inactivation. Nat Genet 9, 316–320 (1995). https://doi.org/10.1038/ng0395-316

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng0395-316

This article is cited by

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