Loss of genomic methylation causes p53-dependent apoptosis and epigenetic deregulation (original) (raw)

References

  1. Wolffe, A.P. & Matzke, M.A. Epigenetics: regulation through repression. Science 286, 481– 486 (1999).
    Article CAS Google Scholar
  2. Bird, A.P. & Wolffe, A.P. Methylation-induced repression—belts, braces, and chromatin. Cell 99, 451– 454 (1999).
    Article CAS Google Scholar
  3. Jaenisch, R. DNA methylation and imprinting: why bother? Trends Genet. 13, 323–329 (1997).
    Article CAS Google Scholar
  4. Lei, H. et al. De novo DNA cytosine methyltransferase activities in mouse embryonic stem cells. Development 122, 3195– 3205 (1996).
    CAS PubMed Google Scholar
  5. Li, E., Bestor, T.H. & Jaenisch, R. Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell 69, 915–926 (1992).
    Article CAS Google Scholar
  6. Okano, M., Bell, D.W., Haber, D.A. & Li, E. DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development . Cell 99, 247–257 (1999).
    Article CAS Google Scholar
  7. Li, E., Beard, C. & Jaenisch, R. Role for DNA methylation in genomic imprinting. Nature 366, 362–365 ( 1993).
    Article CAS Google Scholar
  8. Beard, C., Li, E. & Jaenisch, R. Loss of methylation activates Xist in somatic but not in embryonic cells. Genes Dev. 9, 2325– 2334 (1995).
    Article CAS Google Scholar
  9. Panning, B. & Jaenisch, R. DNA hypomethylation can activate Xist expression and silence X-linked genes. Genes Dev. 10, 1991–2002 (1996).
    Article CAS Google Scholar
  10. Stancheva, I. & Meehan, R.R. Transient depletion of xDnmt1 leads to premature gene activation in Xenopus embryos. Genes Dev. 14, 313–327 (2000).
    CAS PubMed PubMed Central Google Scholar
  11. Baylin, S.B. & Herman, J.G. DNA hypermethylation in tumorigenesis: epigenetics joins genetics. Trends Genet. 16, 168–174 (2000).
    Article CAS Google Scholar
  12. Jones, P.A. & Laird, P.W. Cancer epigenetics comes of age . Nature Genet. 21, 163– 167 (1999).
    Article CAS Google Scholar
  13. Laird, P.W. et al. Suppression of intestinal neoplasia by DNA hypomethylation . Cell 81, 197–205 (1995).
    Article CAS Google Scholar
  14. Chen, R.Z., Pettersson, U., Beard, C., Jackson-Grusby, L. & Jaenisch, R. DNA hypomethylation leads to elevated mutation rates. Nature 395, 89– 93 (1998).
    Article CAS Google Scholar
  15. Hansen, R.S. et al. The DNMT3B DNA methyltransferase gene is mutated in the ICF immunodeficiency syndrome. Proc. Natl. Acad. Sci. USA 96, 14412–14417 (1999).
    Article CAS Google Scholar
  16. Xu, G.L. et al. Chromosome instability and immunodeficiency syndrome caused by mutations in a DNA methyltransferase gene. Nature 402 , 187–191 (1999).
    Article CAS Google Scholar
  17. Sauer, B. & Henderson, N. Site-specific DNA recombination in mammalian cells by the Cre recombinase of bacteriophage P1. Proc. Natl. Acad. Sci. USA 85, 5166– 5170 (1988).
    Article CAS Google Scholar
  18. Margot, J.B. et al. Structure and function of the mouse DNA methyltransferase gene: Dnmt1 shows a tripartite structure. J. Mol. Biol. 297, 293–300 (2000).
    Article CAS Google Scholar
  19. Onishi, M. et al. Applications of retrovirus-mediated expression cloning. Exp. Hematol. 24, 324–329 (1996).
    CAS PubMed Google Scholar
  20. Levine, A.J. p53, the cellular gatekeeper for growth and division. Cell 88, 323–331 (1997).
    Article CAS Google Scholar
  21. Hakem, R., de la Pompa, J.L., Elia, A., Potter, J. & Mak, T.W. Partial rescue of Brca1 (5-6) early embryonic lethality by p53 or p21 null mutation. Nature Genet. 16, 298–302 ( 1997).
    Article CAS Google Scholar
  22. Lim, D.S. & Hasty, P. A mutation in mouse rad51 results in an early embryonic lethal that is suppressed by a mutation in p53. Mol. Cell. Biol. 16, 7133–7143 (1996).
    Article CAS Google Scholar
  23. Ludwig, T., Chapman, D.L., Papaioannou, V.E. & Efstratiadis, A. Targeted mutations of breast cancer susceptibility gene homologs in mice: lethal phenotypes of Brca1, Brca2, Brca1/Brca2, Brca1/p53, and Brca2/p53 nullizygous embryos. Genes Dev. 11, 1226– 1241 (1997).
    Article CAS Google Scholar
  24. Jacks, T. et al. Tumor spectrum analysis in p53-mutant mice. Curr. Biol. 4, 1–7 ( 1994).
    Article CAS Google Scholar
  25. Emerman, M. & Temin, H.M. Genes with promoters in retrovirus vectors can be independently suppressed by an epigenetic mechanism. Cell 39, 449–467 ( 1984).
    Article CAS Google Scholar
  26. Leonhardt, H., Page, A.W., Weier, H.U. & Bestor, T.H. A targeting sequence directs DNA methyltransferase to sites of DNA replication in mammalian nuclei . Cell 71, 865–873 (1992).
    Article CAS Google Scholar
  27. Chuang, L.S. et al. Human DNA-(cytosine-5) methyltransferase-PCNA complex as a target for p21WAF1. Science 277, 1996– 2000 (1997).
    Article CAS Google Scholar
  28. Fambrough, D., McClure, K., Kazlauskas, A. & Lander, E.S. Diverse signaling pathways activated by growth factor receptors induce broadly overlapping, rather than independent, sets of genes. Cell 97, 727–741 (1999).
    Article CAS Google Scholar
  29. Bird, A. & Tweedie, S. Transcriptional noise and the evolution of gene number. Philos. Trans. R. Soc. Lond. B. Biol. Sci. 349, 249–253 (1995).
    Article CAS Google Scholar
  30. Yoder, J.A., Walsh, C.P. & Bestor, T.H. Cytosine methylation and the ecology of intragenomic parasites. Trends Genet. 13, 335– 340 (1997).
    Article CAS Google Scholar
  31. Fan, G.P. et al. DNA hypomethyation perturbs the function and survival of CNS neurons in postnatal animals. J. Neurosci. (in press).
  32. Sabapathy, K., Klemm, M., Jaenisch, R. & Wagner, E.F. Regulation of ES cell differentiation by functional and conformational modulation of p53 . EMBO J. 16, 6217–6229 (1997).
    Article CAS Google Scholar
  33. Hermeking, H. & Eick, D. Mediation of c-Myc-induced apoptosis by p53. Science 265, 2091– 2093 (1994).
    Article CAS Google Scholar
  34. Hendrich, B. & Bird, A. Identification and characterization of a family of mammalian methyl-CpG binding proteins. Mol. Cell. Biol. 18, 6538–6547 ( 1998).
    Article CAS Google Scholar
  35. Michaelson, J.S., Bader, D., Kuo, F., Kozak, C. & Leder, P. Loss of Daxx, a promiscuously interacting protein, results in extensive apoptosis in early mouse development. Genes Dev. 13, 1918–1923 (1999).
    Article CAS Google Scholar
  36. Walsh, C.P., Chaillet, J.R. & Bestor, T.H. Transcription of IAP endogenous retroviruses is constrained by cytosine methylation. Nature Genet. 20, 116–117 (1998).
    Article CAS Google Scholar
  37. Marahrens, Y., Panning, B., Dausman, J., Strauss, W. & Jaenisch, R. Xist-deficient mice are defective in dosage compensation but not spermatogenesis. Genes Dev. 11, 156–166 (1997).
    Article CAS Google Scholar
  38. Cormier, R.T. & Dove, W.F. Dnmt1N/+ reduces the net growth rate and multiplicity of intestinal adenomas in C57BL/6-multiple intestinal neoplasia (Min)/+ mice independently of p53 but demonstrates strong synergy with the modifier of Min 1(AKR) resistance allele. Cancer Res. 60, 3965–3970 (2000).
    CAS PubMed Google Scholar
  39. Rhee, I. et al. CpG methylation is maintained in human cancer cells lacking DNMT1 . Nature 404, 1003–1007 (2000).
    Article CAS Google Scholar
  40. Knox, J.D. et al. Inhibition of DNA methyltransferase inhibits DNA replication . J. Biol. Chem. 275, 17986– 17990 (2000).
    Article CAS Google Scholar
  41. Fuks, F., Burgers, W.A., Brehm, A., Hughes-Davies, L. & Kouzarides, T. DNA methyltransferase Dnmt1 associates with histone deacetylase activity. Nature Genet. 24, 88–91 (2000).
    Article CAS Google Scholar
  42. Robertson, K.D. et al. DNMT1 forms a complex with rb, E2F1 and HDAC1 and represses transcription from E2F-responsive promoters. Nature Genet. 25, 338–342 (2000).
    Article CAS Google Scholar
  43. Rountree, M.R., Bachman, K.E. & Baylin, S.B. DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at replication foci. Nature Genet. 25 , 269–277 (2000).
    Article CAS Google Scholar
  44. Bird, A. Does DNA methylation control transposition of selfish elements in the germline? Trends Genet. 13, p469– 472 (1997).
    Article Google Scholar
  45. Yoder, J.A., Walsh, C.P. & Bestor, T.H. Cytosine methylation and the ecology of intragenomic parasites. Trends Genet. 13, 335– 340 (1997).
    Article CAS Google Scholar
  46. Walsh, C.P. & Bestor, T.H. Cytosine methylation and mammalian development. Genes Dev. 13, 26– 34 (1999).
    Article CAS Google Scholar
  47. Colosi, P., Talamantes, F. & Linzer, D.I. Molecular cloning and expression of mouse placental lactogen I complementary deoxyribonucleic acid. Mol. Endocrinol. 1, 767–776 ( 1987).
    Article CAS Google Scholar
  48. Ruggiu, M. et al. The mouse Dazla gene encodes a cytoplasmic protein essential for gametogenesis. Nature 389, 73– 77 (1997).
    Article CAS Google Scholar
  49. Jat, P.S., Cepko, C.L., Mulligan, R.C. & Sharp, P.A. Recombinant retroviruses encoding simian virus 40 large T antigen and polyomavirus large and middle T antigens. Mol. Cell. Biol. 6, 1204–1217 (1986).
    Article CAS Google Scholar
  50. O'Gorman, S., Dagenais, N.A., Qian, M. & Marchuk, Y. Protamine-Cre recombinase transgenes efficiently recombine target sequences in the male germ line of mice, but not in embryonic stem cells. Proc. Natl. Acad. Sci. USA 94, 14602–14607 (1997).
    Article CAS Google Scholar
  51. Church, G.M. & Gilbert, W. Genomic sequencing. Proc. Natl. Acad. Sci. USA 81, 1991– 1995 (1984).
    Article CAS Google Scholar
  52. Eisen, M.B., Spellman, P.T., Brown, P.O. & Botstein, D. Cluster analysis and display of genome-wide expression patterns. Proc. Natl. Acad. Sci. USA 95, 14863– 14868 (1998).
    Article CAS Google Scholar
  53. Gaudet, F., Talbot, D., Leonhardt, H. & Jaenisch, R. A short DNA methyltransferase isoform restores methylation in vivo. J. Biol. Chem. 273, 32725–32729 (1998).
    Article CAS Google Scholar

Download references