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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 Genetics volume 2, pages 161–166 (1992)Cite this article

Abstract

To further our understanding of initiation and imprinting of X–chromosome inactivation, we have examined methylation of specific CpG sites of X–linked Pgk–1 and G6pd genes throughout female mouse development. Methylation occurs around the time of inactivation and earlier for Pgk–1, which is closer to the X–inactivation centre. In female primordial germ cells, the inactive X chromosome escapes methylation; this may underly the reversibility of inactivation at meiosis. Similarly, the genes are unmethylated on the inactive X chromosome in sperm; hence, the imprint specifying preferential X–inactivation in extra–embryonic tissues must reside elsewhere.

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References

  1. Lyon, M.F. Gene action in the X chromosome of the mouse (Mus musculus). Nature 190, 372–373 (1961).

    Article  CAS  PubMed  Google Scholar 

  2. 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 

  3. 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 

  4. 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 

  5. Papaioannou, V.E., West, J.D., Bucher, T. & Linke, I.M. Non-random X-chromosome expression early in mouse development. Devl. Genet. 2, 305–315 (1981).

    Article  Google Scholar 

  6. 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 

  7. Gartler, S. M., Rivest, M. & Cole, R.E. Cytological evidence for an inactive X chromosome in murine oogonia. Cytogenet. cell. Genet. 28, 203–207 (1980).

    Article  CAS  PubMed  Google Scholar 

  8. Johnston, P. G. X chromosome activity in female germ cells of mice heterozygous for Searle's translocation, T(X;16)16H. Genet. Res. 37, 317–322 (1981).

    Article  CAS  PubMed  Google Scholar 

  9. Kratzer, P.G. & Chapman, V.M. X-chromosome reactivation in oocytes of Mus caroli. Proc. natn. Acad. Sci. U.S.A. 78, 3093–3097 (1981).

    Article  CAS  Google Scholar 

  10. McMahon, A., Fosten, M. & Monk, M. Random X-chromosome inactivation in female primordial germ cells in the mouse. J. Embryol. exp. Morph. 64, 251–258 (1981).

    CAS  PubMed  Google Scholar 

  11. Monk, M. & McLaren, A. X-chromosome activity in foetal germ cells of the mouse. J. Embryol. exp. Morph. 63, 75–84 (1981).

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  13. Monk, M. & Grant, M. Preferential X-chromosome inactivation, DNA methylation and imprinting. In Genomic Imprinting, Development supplement (eds Monk, M. & Surani) 55–62 (The Company of Biologists, Cambridge, Massachusetts, 1990).

    Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  15. Pfeifer, G. et al. Polymerase chain reaction-aided genomic sequencing of an X chromosome-linked CpG island: Methylation patterns suggest clonal inheritance, CpG site autonomy, and an explanation of activity state stability. Proc. natn. Acad. Sci. U.S.A. 87, 8252–8256 (1990).

    Article  CAS  Google Scholar 

  16. Hansen, R.S., Ellis, N.A. & Gartler, S.M. Demethylation of specific sites in the 5′ region of the inactive X-linked human Pgkgene correlates with the appearance of nuclease sensitivity and gene expression. Molec. cell Biol. 8, 4962–4699 (1988).

    Google Scholar 

  17. Lock, L.F., Takagi, N. & Martin, G.R. Methylation of the HPRT gene on the inactive X occurs after chromosome inactivation. Cell 48, 39–46 (1987).

    Article  CAS  PubMed  Google Scholar 

  18. Singer-Sam, J. et al. Use of an Hpa II-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 

  19. Driscoll, D. J. & Migeon, B. R. Sex difference in methylation of single-copy genes in human meiotic germ cells: implications for X chromosome inactivation, parental imprinting and origin of CpG mutations. Somat Cell molec. Genet. 16, 267–282 (1990).

    Article  CAS  PubMed  Google Scholar 

  20. Singer-Sam, J., Gold stein, L., Dai, A., Gartler, S.M. & Riggs, A.D. A potentially critical Hpa II site of the X chromosome-linked PGK-1 gene is unmethylated prior to the onset of meiosis of human oogenic cells. Proc. natn. Acad. Sci. U.S.A. 89, 1413–1417 (1992).

    Article  CAS  Google Scholar 

  21. 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 

  22. 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 

  23. Toniolo, D. et al. The CpG island in the 5′ region of the G6PD gene of man and mouse. Gene 102, 197–203 (1991).

    Article  CAS  PubMed  Google Scholar 

  24. Solter, D. & Knowles, B.B. Immunosurgery of mouse blastocysts. Proc. natn. Acad. Sci. U.S.A. 72, 5099–5102 (1975).

    Article  CAS  Google Scholar 

  25. Ginsberg, M., Snow, M.H.L. & McLaren, A. Primordial germ cells in the mouse embryo during gastrulation. Development 110, 521–528 (1990).

    Google Scholar 

  26. Bradley, A. & Robertson, E.S. Embryo-derived stem cells: a tool for elucidating the developmental genetics of the mouse. Curr. Topics Devl. Biol. 20, 357–371 (1986).

    Article  CAS  Google Scholar 

  27. Cattanach, B.M. & Papworth, D. Controlling elements in the mouse. V. Linkage tests with X-linked genes. Genet. Res. 38, 57–70 (1981).

    Article  CAS  PubMed  Google Scholar 

  28. Barlett, M.H., Adra, C.N., Park, J., Chapman, V.M. & McBurney, M.W. DNA methylation of two X chromosme genes in female somatic and embryonal carcinoma cells. Somat. Cell. molec. Genet. 17, 35–47 (1991).

    Article  Google Scholar 

  29. Borsani, B. et al. Characterization of a murine gene expressed from the inactive X chromosome. Nature 351, 325–329 (1991).

    Article  CAS  PubMed  Google Scholar 

  30. 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 

  31. Monk, M. (ed.) Mammalian Development - A Practical Approach (IRL Press, Oxford 1987).

    Google Scholar 

  32. McMahon, A., Fosten, M. & Monk, M. X-chromosome inactivation mosaicism in the three germ layers and the germ line of the mouse embryo. J. Embryol. exp. Morph. 74, 207–220 (1983).

    CAS  PubMed  Google Scholar 

  33. Chiquoine, A.D. The identification, origin and migration of primordial germ cells of the mouse embryo. Anat Rec. 118, 135–146 (1954).

    Article  CAS  PubMed  Google Scholar 

  34. Reik, W., Collick, A., Norris, M.L., Barton, S.C. & Surani, M.A. Genomic imprinting determines methylation of parental alleles in transgenic mice. Nature 326, 248–251 (1987).

    Article  Google Scholar 

  35. Jeanpierre, M. A rapid method for the purification of DNA from blood. Nucl. Acids Res. 15, 964 (1987).

    Article  Google Scholar 

  36. McClelland, M., Hanish, J., Nelson, M. & Patel, Y. KGB: a single buffer for all restriction endonucleases. Nucl. Acids Res. 16, 364 (1988).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Beck, B. N. & Ho, S. N. Increased specificity of PCR-amplified products by size-fractionation of restriction-enzyme digested template genomic DNA. Nucl. Acids Res. 16, 9051 (1988).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. MRC Mammalian Development Unit, Wolfson House, University College London, Stephenson Way, London, NW1 2HE, UK

    Mark Grant, Maurizio Zuccotti & Marilyn Monk

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

    Maurizio Zuccotti

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  3. Marilyn Monk
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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. Nat Genet 2, 161–166 (1992). https://doi.org/10.1038/ng1092-161

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