Abstract
Single copy probes derived from CpG-rich island clones fromEag I andNot I linking libraries and nine rare-cutter restriction endonucleases were used to investigate the methylation status of CpG-rich islands on the inactive and active X chromosomes (Chr) of the mouse. Thirteen of the 14 probes used detected CpG-rich islands in genomic DNA. The majority of island CpGs detected by rare-cutter restriction endonucleases were methylated on the inactive X Chr and unmethylated on the active X Chr, but some heterogeneity within the cell population used to make genomic DNA was detected. The CpG-rich islands detected by two putative pseudoautosomal probes remained unmethylated on both the active and inactive X Chrs. Otherwise, distance from the X Chr inactivation center did not affect the methylation profile of CpG-rich islands. We conclude that methylation of CpG-rich islands is a general feature of X Chr inactivation.
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Avner, P., Arnaud, D., Amar, L., Cambrou, J., Winking, H. and Russell, L.B.: Characterization of a panel of somatic cell hybrids for regional map** of the mouse X chromosome.Proc Natl Acad Sci USA 84: 5330–5334, 1987.
Bird, A.P.: CpG-rich islands and the function of DNA methylation.Nature 321: 209–213, 1986.
Bird, A.P.: CpG islands as gene markers in the vertebrate nucleus.Trends Genet 3: 342–347, 1987.
Bird, A.P., Taggart, M., Frommer, N., Miller, O.J. and Macleod, D.: A fraction of the mouse genome that is derived from islands of non-methylated CpG rich DNA.Cell 40: 91–99 1985.
Brockdorff, N., Montague, M., Smith, S. and Rastan, S.: Construction and analysis of linking libraties from the mouse X chromosome.Genomics 7: 573–578, 1990.
Brown, W.R.A. and Bird, A.P.: Long-range restriction map** of mammalian genomic DNA.Nature 322: 477–481, 1986.
Cattanach, B.M., Evans, E.P., Burtenshaw, M.D. and Barlow, J.: Male, female and intersex development in mice of identical chromosome constitution.Nature, 300: 445–446, 1982.
Ellis, N. and Goodfellow, P.N.: The mammalian pseudoautosomal region.Trends Genet 5: 406–410, 1989.
Goodfellow, P.J., Mondello, C., Darling, S.M., Pym, B., Little, P. and Goodfellow, P.N.: Absence of methylation of a CpG-rich region at the 5′ end of theMIC2 gene on the active X, the inactive X and the Y chromosome.Proc Natl Acad Sci USA 85: 5605–5609, 1988.
Gardiner-Garden, M. and Frommer, M.: CpG islands in vertebrate genomes.J Mol Biol 196: 261–282, 1987.
Hansen, R.S., Ellis, N.A. and Gartler, S.M.: Demethylation of specific sites in the 5′ region of the inactive X-linked humanphosphoglycerate kinase gene correlates with the appearance of nuclease sensitivity and gene expression.Mol Cell Biol 8: 4692–4699, 1988.
Lock, L.F., Melton, D.W., Caskey, C. and Martin, G.R.: Methylation of the mouseHprt gene differs on the active and inactive X chromosome.Mol Cell Biol 6: 914–924, 1986.
Lock, L.F., Takagi, N. and Martin, G.R.: Methylation of theHprt gene on the inactive X occurs after chromosome inactivation.Cell 48: 39–46, 1987
Lyon, M.F.: Gene action in the X chromosome of the mouseMus musculus L.Nature 190: 372–373, 1961.
McLaren, A. and Monk, M.: Fertile females produced by inactivation of an X chromosome of “sex reversed” mice.Nature 300: 446–448, 1982.
Miller, D.A., Okamoto, E., Erlanger, B.F. and Miller, O.J.: Is DNA methylation responsible for mammalian X chromosome inactivation?Cytogenet Cell Genet 33: 345–349, 1982.
Mohandas, T., Sparkes, R.S. and Shapiro, L.J.: Reactivation of an inactive human X chromosome: Evidence for X-inactivation by DNA methylation.Science 211: 393–396, 1981.
Monk, M.: Methylation and the X chromosome.Bioessays 4: 204–208, 1986.
Rastan, S.: Non-random inactivation in mouse X-autosome translocation embryos—location of the inactivation center.J Embryol Exp Morph 78: 1–22, 1983.
Rastan, S. and Brown, S.D.M.: The search for the mouse X chromosome inactivation center.Genet Res, in press 1990.
Riggs, A.D., Singer-Sam, J. and Keith, D.H.: Methylation of the PGK promotor region and an enhancer way-station model for X chromosome inactivation.In G.-L. Cantoni and A. Razin (eds.);Biochemistry and Biology of DNA Methylation, Liss, New York, 1985.
Toniolo, D., Martini, G., Migeon, B.R. and Dono, R.: Expression of theG6PD locus on the human X chromosome is associated with demethylation of three CpG islands within 100 kb of DNA.EMBO J 7: 401–406, 1988.
Venolia, L. and Gartler, S.M.: Comparison of transformation efficiency of human active and inactive X chromosomal DNA.Nature 302: 82–83, 1983.
Wolf, S.F. and Migeon, B.R.: Studies of X chromosome DNA methylation in normal human cells.Nature, 295: 667–671, 1982.
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Norris, D.P., Brockdorff, N. & Rastan, S. Methylation status of CpG-rich islands on active and inactive mouse X chromosomes. Mammalian Genome 1, 78–83 (1991). https://doi.org/10.1007/BF02443782
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DOI: https://doi.org/10.1007/BF02443782