Abstract
Studies of methylation along 28 kilobases of X-chromosome DNA, assayed by Southern blot analysis using cloned X-chromosome-specific probes, indicates that XDNA methylation in normal human cells changes with replication, is not correlated with number of X chromosomes or transcriptional activity, and is less stable and more prevalent than when the human X is in the foreign environment of mouse–human hybrid cells. In contrast with observations of others in heteroploid cells, we observed no derepression of the inactive X in clonal populations of normal human fibroblasts treated with 5-azacytidine. This may reflect the differences in stability of the methylation of the human X in a foreign environment. Our observations preclude ubiquitous methylation differences as the molecular basis for X-chromosome inactivation.
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References
Holliday, R. & Pugh, J. E. Science 187, 227–232 (1975).
Sager, R. & Kitchin, R. Science 184, 426–433 (1978).
Riggs, A. D. Cytogenet Cell Genet. 14, 9–25 (1975).
Lyon, Mary F. Biol. Rev. 47, 1–35 (1972).
Ehrlich, M. & Wang, R. Y-H. Science 212, 1350–1357 (1981).
Razin, A. & Riggs, A. D. Science 210, 604–610 (1980).
Liskay, R. M. & Evans, R. J. Proc. natn. Acad. Sci. U.S.A. 77, 4895–4898 (1980).
Comings, D. C. Expl Cell Res. 74, 383–390 (1972).
McGhee, J. D. & Ginder, G. D. Nature 280, 419–420 (1979).
Mandel, J. L. & Chambon, P. Nucleic Acids Res. 7, 2081–2103 (1979).
van der Ploeg, L. H. T. & Flavell, R. A. Cell 19, 947–958 (1980).
Shen, C. K. J. & Maniatis, T. Proc. natn. Acad. Sci. U.S.A. 77, 6634–6638 (1980).
Pollock, Y., Stein, R., Ragin, A. & Cedar, H. Proc. natn. Acad. Sci. U.S.A. 77, 6463–6467 (1980).
Wigler, M., Levy, D. & Perucho, M. Cell 24, 33–40 (1981).
Singer, J., Roberts-Ems, J., Luthardt, F. W. & Riggs, A. D. Nucleic Acids Res. 7, 2369–2385 (1979).
Groudine, M., Eisenman, R. & Weintraub, H. Nature 292, 311–317 (1981).
Compere, S. J. & Palmiter, R. D. Cell 25, 233–240 (1981).
Mohandas, T., Sparkes, R. S. & Shapiro, L. J. Science 211, 393–396 (1980).
Wolf, S. F., Mareni, C. E. & Migeon, B. R. Cell 21, 95–102 (1980).
Waalwijk, C. & Flavell, R. A. Nucleic Acids Res. 12, 4631–4641 (1978).
Scott, A. F., Phillips, J. A. & Migeon, B. R. Proc. natn. Acad. Sci. U.S.A. 76, 4563–4565 (1979).
Migeon, B. R., Brown, T., Axelman, J. & Migeon, C. J. Proc. natn. Acad. Sci. U.S.A. 78, 6339–6343 (1981).
Benton, D. W. & Davis, R. W. Science 196, 1980–1982 (1977).
Lawn, R. M. et al. Cell 15, 1157–1174 (1978).
Migeon, B. R., Sprenkle, J. A. & Do, T. T. Cell 18, 637–641 (1979).
Taylor, S. M. & Jones, P. A. Cell 17, 771–779 (1979).
Jones, P. A. & Taylor, S. M. Cell 20, 85–93 (1980).
Kahan, B. & DeMars, R. Proc. natn. Acad. Sci. U.S.A. 72, 1510–1514 (1975).
Clough, W. D. & Davidson, R. L. Science (in the press).
Wolf, S. F. & Schlessinger, D. Biochemistry 16, 2783–2791 (1977).
Southern, E. M. J. molec. Biol. 98, 503–517 (1975).
Migeon, B. R., Wolf, S. F., Mareni, C. E. & Axelman, J. (in preparation).
Wilson, J. T. et al. Nucleic Acids Res. 5, 563–581 (1978).
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Wolf, S., Migeon, B. Studies of X chromosome DNA methylation in normal human cells. Nature 295, 667–671 (1982). https://doi.org/10.1038/295667a0
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DOI: https://doi.org/10.1038/295667a0
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