Abstract
ANIMAL somatic cell DNA is characterized by a bimodal pattern of methylation: tissue-specific genes are methylated in most cell types whereas housekeeping genes have 5′ CpG islands which are constitutively unmethylated1,2. Because methyl moieties derived from the gametes are erased in the morula and early blastula3, this profile must be re-established in every generation; this is apparently accomplished by a wave of non-CpG island de novo methylation that occurs at implantation4. Using transfection into embryonic stem cells and transgenic mice as a model system, we now show that Spl elements play a key role in protecting a CpG island in the adenine phosphor!bosyItransferase (APRT) gene from de novo methylation. This recognition mechanism represents a critical step in embryogenesis, as it is responsible for setting up the correct genome methylation pattern which, in turn, is involved in regulating basal gene expression in the organism5.
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References
Bird, A. P. Nature 321, 209–213 (1986).
Yisraeli, J. & Szyf, M. DNA Methylation: Biochemistry and Biological Significance (eds Razin, A., Cedar, H. & Riggs, A. D.) 353–378 (Springer, New York, 1984).
Monk, M., Boubelik, M. & Lehnert, S. Development 99, 371–382 (1987).
Kafri, T. et al. Genes Dev. 6, 705–714 (1992).
Eden, S. & Cedar, H. Curr. Opin. Genet. Dev. 4, 255–259 (1994).
Frank, D. et al. Nature 351, 239–241 (1991).
Szyf, M., Tonigawa, G. & McCarthy, P. L. J. Molec. cell. Biol. 10, 4396–4400 (1990).
Shemer, R., Eisenberg, S., Breslow, J. L. & Razin, A. J. biol. Chem. 266, 23676–23681 (1991).
Choi, Y. C. & Chae, C. B. Molec. cell. Biol. 13, 5538–5548 (1993).
Kolsto, A. B. et al. Nucleic Acids Res. 14, 9667–9678 (1986).
Jahner, D. et al. Nature 298, 623–628 (1982).
Mummaneni, P., Bishop, P. L. & Turker, M. S. J. biol. Chem. 268, 552–558 (1993).
Gardiner-Garden, M. & Frommer, M. J. molec. Biol. 196, 261–282 (1987).
Holler, M., Westin, G., Jiriany, J. & Schaffner, W. Genes Dev. 2, 1127–1135 (1988).
van der Ploeg, L. H. T. & Flavell, R. A. Cell 19, 947–958 (1980).
Cedar, H. et al. Cold Spring Harb. Symp. quant. Biol. 47, 605–609 (1983).
Briggs, M. R., Kadonaga, J. T., Bell, S. P. & Tjian, R. Science 234, 47–52 (1986).
Pfeifer, G. P., Tanguay, R. L., Steigerwald, S. D. & Riggs, A. D. Genes Dev. 4, 1277–1287 (1990).
Razin, A. & Cedar, H. Cell 77, 473–476 (1994).
Lock, L. F., Takagi, N. & Martin, G. R. Cell 48, 39–46 (1987).
Stoger, R. et al. Cell 73, 61–71 (1993).
Lichtenstein, M., Keini, G., Cedar, H. & Bergman, Y. Cell 76, 913–923 (1994).
Lowy, I. et al. Cell 22, 817–823 (1980).
Felgner, P. L. et al. Proc. natn. Acad. Sci. U.S.A. 84, 7413–7414 (1987).
Jones, K. A., Kadonaga, T., Luciw, P. A. & Tjian, R. Science 232, 755–759 (1986).
Deng, W. P. & Nickoloff, J. A. Analyt. Biochem. 200, 81–88 (1992).
Hogan, B., Constantini, F. & Lacy, E. Manipulating the Mouse Embryo (Cold Spring Harbor Laboratory, New York, 1986).
Macleod, D., Charlton, J., Mullins, J. & Bird, A. P. Genes Dev. (in the press).
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Brandeis, M., Frank, D., Keshet, I. et al. Spl elements protect a CpG island from de novo methylation. Nature 371, 435–438 (1994). https://doi.org/10.1038/371435a0
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DOI: https://doi.org/10.1038/371435a0
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