Abstract
The mechanism for establishing the DNA methylation patterns observed in adult mammalian tissues is not well understood. To determine when adult patterns are established for housekeeping genes, we examined the clustered CpGs in genes on the human active X chromosome (PGK, G6PD, P3, GdX, HPRT) and the autosomal gene,DHFR. We find unique methylation patterns present at theP3 locus in all tissues analyzed from 6- to 9-week fetal specimens, and at theHPRT locus in adrenal gland DNA at this stage of development. Adult patterns are established subsequently by demethylating specific CpGs. Our results show that demethylating events affecting CpG islands are programmed during mammalian fetal development. They suggest that the process of de novo methylation in the fetus methylates at least some sites in the 3′ region of the CpG islands in active genes and that adult patterns are established at 6–14 weeks developmental age by sequence-specific demethylation.
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Driscoll, D.J., and Migeon, B.R. (1990).Somat. Cell Mol. Genet. 16267–282.
Monk, M., Boubelik, M., and Lehnert, S. (1987).Development 99371–382.
Sanford, J.P., Clark, H.J., Chapman, V.M., and Rossant, J. (1987).Genes Dev. 11039–1046.
Sanford, J.P., Forrester, L., Chapman, V., Chandley, A., and Hastie, N. (1984).Nucleic Acids Res. 122823–2836.
Swain, J.L., Stewart, T.A., and Leder, P. (1987).Cell 50719–727.
Trasler, J.M., Hake, L.E., Johnson, P.A., Alcivar, A.A., Millette, C.F., and Hecht, N.B. (1990).Mol. Cell Biol. 101828–1834.
Jahner, D., and Jaenisch, R. (1984). InDNA Methylation Biochemistry and Biological Significance (ed.) Razin, A., Cedar, H., and Riggs, A.D. (Springer-Verlag, New York), pp. 189–219.
Bird, A.P. (1986).Nature 321209–213.
Kaslow, D.C., and Migeon, B.R. (1987).Proc. Natl. Acad. Sci. U.S.A. 846210–6214.
Migeon, B.R. (1990).Genet. Res. 5691–98.
Lock, L.F., Takagi, N., and Martin, G.R. (1987).Cell 4839–46.
Singer-Sam, J., Grant, M., LeBon, J.M., Okuyama, K., Chapman, V., Monk, M., and Riggs, A.D. (1990).Mol. Cell Biol. 104987–4989.
Migeon, B.R., Jan de Beur, S., and Axelman, J., (1989).Exp. Cell Res. 182597–609.
Toniolo, D., D'Urso, M., Martini, G., Persico, M.G., Tufano, V., Battistuzzi, G., and Luzzatto, L. (1984).EMBO J. 31987–1995.
Wolf, S.F., Dintzis, S., Toniolo, D., Persico, G., Lunnen, K.D., Axelman, J., and Migeon, B.R. (1984).Nucleic 129333–9348.
Toniolo, D., Martini, G., Migeon, B.R., and Dono, R. (1988).EMBO J. 7401–406.
Wolf, S.F., Jolly, D.J., Lunnen, K.D., Friedmann, T., and Migeon, B.R. (1984).Proc. Natl. Acad. Sci. U.S.A. 812806–2810.
Yen, P.H., Patel, P., Chinault, A.C., Mohandas, T., and Shapiro, L.J. (1984).Proc. Natl. Acad. Sci. U.S.A. 811759–1763.
Alcalay, M., and Toniolo, D. (1988).Nucleic Acids Res. 169527–9543.
Keith, D.H., Singer-Sam, J., and Riggs, A.D. (1986).Mol. Cell. Biol. 64122–4125.
Hansen, R.S., Ellis, N.A., and Gartler, S.M. (1988).Mol. Cell. Biol. 84692–4699.
Chen, M.-J., Shimada, T., Moulton, A.T., Cline, A., Humphries, R.K., Maizel, J., and Nienhuis, A.W. (1984).J. Biol. Chem. 259(6):3933–3943.
Ruta Cullen, C., Hubberman, P., Kaslow, D.C., and Migeon, B.R. (1986).EMBO J. 52223–2229.
Yisraeli, J., and Szyf, M. (1984). InDNA Methylation: Biochemistry and Biological Significance (eds.) Razin, A., Cedar, H., and Riggs, A.D. (Springer-Verlag, New York), pp. 353–378.
Frank, D., Lichtenstein, M., Paroush, Z., Bergman, Y., Shani, M., Razin, A., and Cedar, H. (1990).Phil. Trans. R. Soc. London B. 326241–251.
Beggs, A.H., Axelman, J., and Migeon, B.R. (1986).Somat. Cell Mol. Genet. 12(6):585–594.
Adams, R.L.P. (1990).Biochem J. 265309–320.
Yoo, H., Noshari, J., and Lapeyre, J.N. (1987).J. Biol. Chem. 2628066–8070.
Razin, A., Szyf, M., Kafri, T., Roll, M., Giloh, H., Scarpa, S., Carotti, D., and Cantoni, G.C. (1986).Proc. Natl. Acad. Sci. U.S.A. 832827–2831.
Kautiainen, T.L., and Jones, P.A. (1985).Biochemistry 241193–1196.
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Migeon, B.R., Holland, M.M., Driscoll, D.J. et al. Programmed demethylation in CpG islands during human fetal development. Somat Cell Mol Genet 17, 159–168 (1991). https://doi.org/10.1007/BF01232973
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DOI: https://doi.org/10.1007/BF01232973