Methylation Dynamics in the Early Mammalian Embryo: Implications of Genome Reprogramming Defects for Development

Abstract

In mouse and most other mammalian species, the paternal and maternal genomes undergo parent-specific epigenetic reprogramming during preimplantation development. The paternal genome is actively demethylated within a few hours after fertilization in the mouse, rat, pig, bovine, and human zygote, whereas the maternal genome is passively demethylated by a replication-dependent mechanism after the two-cell embryo stage. These genome-wide demethylation waves may have a role in reprogramming of the genetically inactive sperm and egg chromatin for somatic development. Disturbances in this highly coordinated process may contribute to developmental failures and defects inmammals. The frequency and severity of abnormal phenotypes increase after interferingwith or bypassing essential steps of gametogenesis, early embryogenesis, or both. Nevertheless, it is plausible that normal fertilization, assisted reproduction, and embryo cloning are all susceptible to similar dysregulation of epigenetic components. Although themousemay be an excellentmodel for early human development, species and strain differences in the molecular and cellular events shortly after fertilization may have important implications for the efficiency of epigenetic reprogramming and the incidence of reprogramming defects. Some species, i.e., rabbit and sheep, do not require drastic genome-wide demethylation for early development, most likely because the transition from maternal to embryonic control occurs relatively late during preimplantation development. A better understanding of key reprogramming factors—in particular the demethylase activity in the fertilized egg—is crucial for improving human infertility treatment and the efficiency of mammalian embryo cloning.

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References

  1. Adenot PG, Mercier Y, Renard J-P, Thompson EM (1997) Differential H4 acetylation of paternal andmaternal chromatin precedes DNA replication and differential transcriptional activity in pronuclei of 1-cellmouse embryos. Development 124:4615–4625PubMedGoogle Scholar
  2. Bartolomei MS, Tilghman SM (1997) Genomic imprinting in mammals. Annu Rev Genet 31:493–525PubMedCrossRefGoogle Scholar
  3. Barton SC, Arney KL, Shi W, Fundele R, Surani MA, Haaf T (2001) Genome-wide methylation patterns in normal and uniparental early mouse embryos. Hum Mol Genet 10:2983–2987PubMedCrossRefGoogle Scholar
  4. Beaujean N, Hartshorne G, Cavilla J, Taylor JE, Gardner J, Wilmut I, Meehan R, Young L (2004a) Non-conservation of mammalian preimplantation methylation dynamics. Curr Biol 14:R266–R267PubMedCrossRefGoogle Scholar
  5. Beaujean N, Taylor JE, McGarry M, Gardner JO, Wilmut I, Loi P, Ptak G, Galli C, Lazzari G, Bird A, Young LE, Meehan RR (2004b) The effect of interspecific oocytes on demethylation of sperm DNA. Proc Natl Acad Sci USA 101:7636–7640PubMedCrossRefGoogle Scholar
  6. Bestor TH (2000) The DNA methyltransferases of mammals. Hum Mol Genet 9:2395–2402PubMedCrossRefGoogle Scholar
  7. Bortvin A, Eggan K, Skaletsky H, Akutsu H, Berry DL, Yanagimachi R, Page DC, Jaenisch R (2003) Incomplete reactivation of Oct4-related genes inmouseembryos cloned from somatic nuclei. Development 130:1673–1680PubMedCrossRefGoogle Scholar
  8. Bourc’his D, Le Bourhis D, Patin D, Niveleau A, Comizzoli P, Renard JP, Viegas-Pequignot E (2001) Delayed and incomplete reprogramming of chromosome methylation patterns in bovine cloned embryos. Curr Biol 11:1542–1546PubMedCrossRefGoogle Scholar
  9. Cardoso MC, Leonhardt H (1999) DNA methyltransferase is actively retained in the cytoplasm during early development. J Cell Biol 147:25–32PubMedCrossRefGoogle Scholar
  10. Cowell IG, Aucott R, Mahadevaiah SK, Burgoyne PS, Huskisson N, Bongiorni S, Prantera G, Fanti L, Pimpinelli S, Wu R, Gilbert DM, Shi W, Fundele R, Morrison H, Jeppesen P, Singh P (2002) Heterochromatin, HP1 and methylation at lysine 9 of histone H3 in animals. Chromosoma 111:22–36PubMedCrossRefGoogle Scholar
  11. Dean W, Santos F, Stojkovic M, Zakhartchenko V, Walter J, Wolf E, Reik W (2001) Conservation of methylation reprogramming in mammalian development: aberrant reprogramming in cloned embryos. Proc Natl Acad Sci USA 98:13734–13738PubMedCrossRefGoogle Scholar
  12. Haaf T (2001) The battle of the sexes after fertilization: behaviour of paternal and maternal chromosomesinthe earlymammalianembryo. Chromosome Res 9:263–271PubMedCrossRefGoogle Scholar
  13. Haaf T, Shi W, Fundele R, Arney KL, Surani MA, Barton SC (2004) Differential demethylation of paternal and maternal genomes in the preimplantation mouse embryo: implications formammalian development. In: Schmid M, Nanda I (eds) Chromosomes today, vol. 14. Kluwer Academic Publishers, Dordrecht, Boston, London, pp 207–214Google Scholar
  14. Humpherys D, Eggan K, Akutsu H, Friedman A, Hochedlinger K, Yanagimachi R, Lander ES, Golub TR, Jaenisch R (2002) Abnormal gene expression in cloned mice derived from embryonic stem cell and cumulus cell nuclei. Proc Natl Acad Sci USA 99:12889–12894PubMedCrossRefGoogle Scholar
  15. Jaenisch R, Bird A (2003) Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat Genet 33:245–254PubMedCrossRefGoogle Scholar
  16. Kanka J (2003) Gene expression and chromatin structure in the pre-implantation embryo. Theriogenology 59:3–19PubMedCrossRefGoogle Scholar
  17. Koshla S, Dean W, Brown D, Reik W, Feil R (2001) Culture of preimplantation mouse embryos affects fetal development and the expression of imprinted genes. Biol Reprod 64:918–926CrossRefGoogle Scholar
  18. Ludwig M, Katalinic A, Groß S, Sutcliffe A, Varon R, Horsthemke B (2005) Increased prevalence of imprinting defects in patients with Angelman syndrome born to subfertile couples. J Med Genet 42:289–291PubMedCrossRefGoogle Scholar
  19. Maher ER, Brueton LA, Bowdin SC, Luharia A, Cooper W, Cole TR, Macdonald F, Sampson JR, Barrat CL, Reik W, Hawkins MM (2003) Beckwith-Wiedemann syndrome and assisted reproductive technology (ART). J Med Genet 40:62–64PubMedCrossRefGoogle Scholar
  20. Manes C (1973) The participation of the embryonic genome during early cleavage in the rabbit. Dev Biol 32:453–459PubMedCrossRefGoogle Scholar
  21. Mann MR, Chung YG, Nolen LD, Verona RI, Latham KE, Bartolomei MS (2003) Disruption of imprinted gene methylation and expression in cloned preimplantation stage mouse embryos. Biol Reprod 69:902–914PubMedCrossRefGoogle Scholar
  22. Mayer W, Niveleau A, Walter J, Fundele R, Haaf T (2000a) Demethylation of the zygotic paternal genome. Nature 403:501–502PubMedGoogle Scholar
  23. Mayer W, Smith A, Fundele R, Haaf T (2000b) Spatial separation of parental genomes in preimplantation mouse embryos. J Cell Biol 148:629–634PubMedCrossRefGoogle Scholar
  24. McGrath J, Solter D (1984) Completion of mouse embryogenesis requires both the maternal and paternal genomes. Cell 37:179–183PubMedCrossRefGoogle Scholar
  25. Memili E, First NL (2000) Zygotic and embryonic gene expression in cow: a review of timing andmechanisms of early gene expression as compared with other species. Zygote 8:87–96PubMedCrossRefGoogle Scholar
  26. Oswald J, Engemann S, Lane N, Mayer W, Olek A, Fundele R, Dean W, Reik W, Walter J (2000) Active demethylation of the paternal genome in the mouse zygote. Curr Biol 10:475–478PubMedCrossRefGoogle Scholar
  27. Perreault SD (1992) Chromatin remodeling inmammalian zygotes. Mutat Res 296:43–55PubMedGoogle Scholar
  28. Ratnam S, Mertineit C, Ding F, Howell CY, Clarke HJ, Bestor TH, Chaillet JR, Trasler JM (2002) Dynamics of Dnmt1 methyltransferase expression and intracellular localization during oogenesis and preimplantation development. Dev Biol 235:304–314CrossRefGoogle Scholar
  29. Reik W, Dean W, Walter J (2001) Epigenetic reprogramming in mammalian development. Science 293:1089–1093PubMedCrossRefGoogle Scholar
  30. Rougier D, Bourc’his D, Gomes DM, Niveleau A, Plachot M, Pàldi A, Viegas-Péquignot E (1998) Chromosome methylation patterns during mammalian development. Genes Dev 12:2108–2113PubMedGoogle Scholar
  31. Santos F, Hendrich B, Reik W, Dean W (2002) Dynamic reprogramming of DNA methylation in the early mouse embryo. Dev Biol 241:172–182PubMedCrossRefGoogle Scholar
  32. Schulz RM(1993) Regulation of zygotic gene activation in themouse. BioEssays 8:531–538Google Scholar
  33. Shi W, Haaf T (2002) Aberrant methylation patterns at the two-cell stage as an indicator of early developmental failure. Mol Reprod Dev 63:329–334PubMedCrossRefGoogle Scholar
  34. Shi W, Zakhartchenko V, Wolf E (2003) Epigenetic reprogramming in mammalian nuclear transfer. Differentiation 71:91–113PubMedCrossRefGoogle Scholar
  35. Shi W, Dirim F, Wolf E, Zakhartchenko V, Haaf T (2004) Methylation reprogramming and chromosomal aneuploidy in in vivo fertilized and cloned rabbit preimplantation embryos. Biol Reprod 71:340–347PubMedCrossRefGoogle Scholar
  36. Solter D (2000) Mammalian cloning: advances and limitations. Nat Rev Genet 1:199–207PubMedCrossRefGoogle Scholar
  37. Surani MA, Barton SC, Norris ML (1986) Nuclear transplantation in the mouse: heritable differences between parental genomes after activation of the embryonic genome. Cell 45:127–136PubMedCrossRefGoogle Scholar
  38. Wolffe AP, Matzke MA (1999) Epigenetics: regulation through repression. Science 286:481–486PubMedCrossRefGoogle Scholar
  39. Young LE, Fernandes K, McEvoy TG, Butterwith SC, Gutierrez CG, Carolan C, Broadbent PJ, Robinson JJ, Wilmut I, Sinclair KD (2001) Epigenetic change in IGF2R is associated with fetal overgrowth after sheep embryo culture. Nat Genet 27:153–154PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2006

Authors and Affiliations

  1. 1.Johannes Gutenberg-Universität MainzMainzGermany

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