Reproduction, Fertility and Development Reproduction, Fertility and Development Society
Vertebrate reproductive science and technology
RESEARCH ARTICLE

Gamete imprinting: setting epigenetic patterns for the next generation

Jacquetta M. Trasler
+ Author Affliations
- Author Affliations

McGill University-Montreal Children’s Hospital Research Institute and the Departments of Pediatrics, Human Genetics and Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada. Email: jacquetta.trasler@mcgill.ca

Reproduction, Fertility and Development 18(2) 63-69 https://doi.org/10.1071/RD05118
Submitted: 21 September 2005  Accepted: 21 September 2005   Published: 14 December 2005

Abstract

The acquisition of genomic DNA methylation patterns, including those important for development, begins in the germ line. In particular, imprinted genes are differentially marked in the developing male and female germ cells to ensure parent-of-origin-specific expression in the offspring. Abnormalities in imprints are associated with perturbations in growth, placental function, neurobehavioural processes and carcinogenesis. Based, for the most part, on data from the well-characterised mouse model, the present review will describe recent studies on the timing and mechanisms underlying the acquisition and maintenance of DNA methylation patterns in gametes and early embryos, as well as the consequences of altering these patterns.

Extra keywords: assisted reproductive technologies, DNA methylation, embryogenesis, genomic imprinting, germ cells, human, mouse, oogenesis, spermatogenesis.


Acknowledgments

JMT is a William Dawson Scholar of McGill University and a Scholar of the Fonds de la recherche en santé du Québec. This work was supported by grants from the Canadian Institutes of Health Research and the National Institutes of Health (USA).


References

Aapola, U. , Lyle, R. , Krohn, K. , Antonarakis, S. E. , and Peterson, P. (2001). Isolation and initial characterization of the mouse Dnmt3l gene. Cytogenet. Cell Genet. 92, 122–126.
CrossRef | PubMed |

Allegrucci, C. , Denning, C. , Priddle, H. , and Young, L. (2004). Stem-cell consequences of embryo epigenetic defects. Lancet 364, 206–208.
CrossRef | PubMed |

Anway, M. , Cupp, A. S. , Uzuncu, M. , and Skinner, M. K. (2005). Epigenetic transgenerational actions of endocrine disruptors and male infertility. Science 308, 1466–1469.
CrossRef | PubMed |

Bao, S. , Obata, Y. , Carroll, J. , Domecki, I. , and Kono, T. (2000). Epigenetic modifications necessary for normal development are established during oocyte growth in mice. Biol. Reprod. 62, 616–621.
PubMed |

Bestor, T. , Laudano, A. , and Mattaliano, R. (1988). Cloning and sequencing of a cDNA encoding DNA methyltransferase of mouse cells. The carboxyl-terminal domain of the mammalian enzymes is related to bacterial restriction methyltransferases. J. Mol. Biol. 203, 971–983.
CrossRef | PubMed |

Bourc’his, D. , and Bestor, T. H. (2004). Meiotic catastrophe and retrotransposon reactivation in male germ cells lacking Dnmt3L. Nature 431, 96–99.
CrossRef | PubMed |

Bourc’his, D. , Xu, G. L. , Lin, C. S. , Bollman, B. , and Bestor, T. H. (2001). Dnmt3L and the establishment of maternal genomic imprints. Science 294, 2536–2539.
CrossRef | PubMed |

Brandeis, M. , Ariel, M. , and Cedar, H. (1993). Dynamics of DNA methylation during development. Bioessays 15, 709–713.
CrossRef | PubMed |

Chaillet, J. R. , Vogt, T. F. , Beier, D. R. , and Leder, P. (1991). Parental-specific methylation of an imprinted transgene is established during gametogenesis and progressively changes during embryogenesis. Cell 66, 77–83.
CrossRef | PubMed |

Chedin, F. , Lieber, M. R. , and Hsieh, C. L. (2002). The DNA methyltransferase-like protein DNMT3L stimulates de novo methylation by Dnmt3a. Proc. Natl Acad. Sci. USA 99, 16 916–16 921.
CrossRef | PubMed |

Clark, S. J. , Harrison, J. , Paul, C. L. , and Frommer, M. (1994). High sensitivity mapping of methylated cytosines. Nucleic Acids Res. 22, 2990–2997.
PubMed |

Coffigny, H. , Bourgeois, C. , Ricoul, M. , Bernardino, J. , Vilain, A. , Niveleau, A. , Malfoy, B. , and Dutrillaux, B. (1999). Alterations of DNA methylation patterns in germ cells and Sertoli cells from developing mouse testis. Cytogenet. Cell Genet. 87, 175–181.
CrossRef | PubMed |

Cox, G. F. , Burger, J. , Lip, V. , Mau, U. A. , Sperling, K. , Wu, B. L. , and Horsthemke, B. (2002). Intracytoplasmic sperm injection may increase the risk of imprinting defects. Am. J. Hum. Genet. 71, 162–164.
CrossRef | PubMed |

Davis, T. L. , Trasler, J. M. , Moss, S. B. , Yang, G. J. , and Bartolomei, M. S. (1999). Acquisition of the H19 methylation imprint occurs differentially on the parental alleles during spermatogenesis. Genomics 58, 18–28.
CrossRef | PubMed |

Davis, T. L. , Yang, G. J. , McCarrey, J. R. , and Bartolomei, M. S. (2000). The H19 methylation imprint is erased and re-established differentially on the parental alleles during male germ cell development. Hum. Mol. Genet. 9, 2885–2894.
CrossRef | PubMed |

Dean, W. , Bowden, L. , Aitchison, A. , Klose, J. , Moore, T. , Meneses, J. J. , Reik, W. , and Feil, R. (1998). Altered imprinted gene methylation and expression in completely ES cell-derived mouse fetuses: association with aberrant phenotypes. Development 125, 2273–2282.
PubMed |

DeBaun, M. R. , Niemitz, E. L. , and Feinberg, A. P. (2003). Association of in vitro fertilization with Beckwith–Wiedemann syndrome and epigenetic alterations of LIT1 and H19. Am. J. Hum. Genet. 72, 156–160.
CrossRef | PubMed |

Doherty, A. S. , Mann, M. R. , Tremblay, K. D. , Bartolomei, M. S. , and Schultz, R. M. (2000). Differential effects of culture on imprinted H19 expression in the preimplantation mouse embryo. Biol. Reprod. 62, 1526–1535.
PubMed |

Egger, G. , Liang, G. , Aparico, A. , and Jones, P. A. (2004). Epigenetics in human disease and prospects for epigenetic therapy. Nature 429, 457–463.
CrossRef | PubMed |

El Maarri, O. , Seoud, M. , Coullin, P. , Herbiniaux, U. , Oldenburg, J. , Rouleau, G. , and Slim, R. (2003). Maternal alleles acquiring paternal methylation patterns in biparental complete hydatidiform moles. Hum. Mol. Genet. 12, 1405–1413.
CrossRef | PubMed |

Gicquel, C. , Gaston, V. , Mandelbaum, J. , Siffroi, J. P. , Flahault, A. , and Le Bouc, Y. (2003). In vitro fertilization may increase the risk of Beckwith–Wiedemann syndrome related to the abnormal imprinting of the KCNQ1OT1 gene. Am. J. Hum. Genet. 72, 1338–1341.
CrossRef | PubMed |

Goll, M. G. , and Bestor, T. H. (2005). Eukaryotic cytosine methyltransferases. Annu. Rev. Biochem. 74, 481–514.
CrossRef | PubMed |

Hajkova, P. , Erhardt, S. , Lane, N. , Haaf, T. , El Maarri, O. , Reik, W. , Walter, J. , and Surani, M. A. (2002). Epigenetic reprogramming in mouse primordial germ cells. Mech. Dev. 117, 15–23.
CrossRef | PubMed |

Halliday, J. , Oke, K. , Breheny, S. , Algar, E. , and Amor, D. J. (2004). Beckwith–Wiedemann syndrome and IVF: a case-control study. Am. J. Hum. Genet. 75, 526–528.
CrossRef | PubMed |

Hanel, M. L. , and Wevrick, R. (2001). Establishment and maintenance of DNA methylation patterns in mouse Ndn: implications for maintenance of imprinting in target genes of the imprinting center. Mol. Cell. Biol. 21, 2384–2392.
CrossRef | PubMed |

Hata, K. , Okano, M. , Lei, H. , and Li, E. (2002). Dnmt3L cooperates with the Dnmt3 family of de novo DNA methyltransferases to establish maternal imprints in mice. Development 129, 1983–1993.
PubMed |

Hayward, B. E. , De Vos, M. , Judson, H. , Hodge, D. , Huntriss, J. , Picton, H. M. , Sheridan, E. , and Bonthron, D. T. (2003). Lack of involvement of known DNA methyltransferases in familial hydatidiform mole implies the involvement of other factors in establishment of imprinting in the human female germline. BMC Genet. 4, 2.
CrossRef | PubMed |

Helwani, M. N. , Seoud, M. , Zahed, L. , Zaatari, G. , Khalil, A. , and Slim, R. (1999). A familial case of recurrent hydatidiform molar pregnancies with biparental genomic contribution. Hum. Genet. 105, 112–115.
CrossRef | PubMed |

Howell, C. Y. , Bestor, T. H. , Ding, F. , Latham, K. E. , Mertineit, C. , Trasler, J. M. , and Chaillet, J. R. (2001). Genomic imprinting disrupted by a maternal effect mutation in the Dnmt1 gene. Cell 104, 829–838.
CrossRef | PubMed |

Howlett, S. K. , and Reik, W. (1991). Methylation levels of maternal and paternal genomes during preimplantation development. Development 113, 119–127.
PubMed |

Humpherys, D. , Eggan, K. , Akutsu, H. , Hochedlinger, K. , Rideout, W. M. , Biniszkiewicz, D. , Yanigimachi, R. , and Jaenisch, R. (2001). Epigenetic instability in ES cells and cloned mice. Science 293, 95–97.
CrossRef | PubMed |

Judson, H. , Hayward, B. E. , Sheridan, E. , and Bonthron, D. T. (2002). A global disorder of imprinting in the human female germ line. Nature 416, 539–542.
CrossRef | PubMed |

Jue, K. , Bestor, T. H. , and Trasler, J. M. (1995). Regulated synthesis and localization of DNA methyltransferase during spermatogenesis. Biol. Reprod. 53, 561–569.
PubMed |

Kafri, T. , Ariel, M. , Brandeis, M. , Shemer, R. , Urven, L. , McCarrey, J. , Cedar, H. , and Razin, A. (1992). Developmental pattern of gene-specific DNA methylation in the mouse embryo and germ line. Genes Dev. 6, 705–714.
PubMed |

Kaneda, M. , Okano, M. , Hata, K. , Sado, T. , Tsujimoto, N. , Li, E. , and Sasaki, H. (2004). Essential role for de novo DNA methyltransferase Dnmt3a in paternal and maternal imprinting. Nature 429, 900–903.
CrossRef | PubMed |

Khosla, S. , Dean, W. , Brown, D. , Reik, W. , and Feil, R. (2001). Culture of preimplantation mouse embryos affects fetal development and the expression of imprinted genes. Biol. Reprod. 64, 918–926.
PubMed |

Kono, T. , Obata, Y. , Yoshimzu, T. , Nakahara, T. , and Carroll, J. (1996). Epigenetic modifications during oocyte growth correlates with extended parthenogenetic development in the mouse. Nat. Genet. 13, 91–94.
CrossRef | PubMed |

Lane, N. , Dean, W. , Erhardt, S. , Hajkova, P. , Surani, A. , Walter, J. , and Reik, W. (2003). Resistance of IAPs to methylation reprogramming may provide a mechanism for epigenetic inheritance in the mouse. Genesis 35, 88–93.
CrossRef | PubMed |

La Salle, S. , Mertineit, C. , Taketo, T. , Moens, P. B. , Bestor, T. H. , and Trasler, J. M. (2004). Windows for sex-specific methylation marked by DNA methyltransferase expression profiles in mouse germ cells. Dev. Biol. 268, 403–415.
CrossRef | PubMed |

Lee, J. , Inoue, K. , Ono, R. , Ogonuki, N. , Kohda, T. , Kaneko-Ishino, T. , Ogura, A. , and Ishino, F. (2002). Erasing genomic imprinting memory in mouse clone embryos produced from day 11.5 primordial germ cells. Development 129, 1807–1817.
PubMed |

Lees-Murdock, D. J. , De Felici, M. , and Walsh, C. P. (2003). Methylation dynamics of repetitive DNA elements in the mouse germ cell lineage. Genomics 82, 230–237.
CrossRef | PubMed |

Li, J. Y. , Lees-Murdock, D. J. , Xu, G.-L. , and Walsh, C. P. (2004). Timing of establishment of paternal methylation imprints in the mouse. Genomics 84, 952–960.
CrossRef | PubMed |

Lucifero, D. , Mertineit, C. , Clarke, H. J. , Bestor, T. H. , and Trasler, J. M. (2002). Methylation dynamics of imprinted genes in mouse germ cells. Genomics 79, 530–538.
CrossRef | PubMed |

Lucifero, D. , Mann, M. R. , Bartolomei, M. S. , and Trasler, J. M. (2004a). Gene-specific timing and epigenetic memory in oocyte imprinting. Hum. Mol. Genet. 13, 839–849.
CrossRef | PubMed |

Lucifero, D. , Chaillet, J. R. , and Trasler, J. M. (2004b). Potential significance of genomic imprinting defects for reproduction and assisted reproductive technology. Hum. Reprod. Update 10, 3–18.
CrossRef | PubMed |

Ludwig, M. , Katalinic, A. , Gross, S. , Sutcliffe, A. , Varon, R. , and Horsthemke, B. (2005). Increased prevalence of imprinting defects in patients with Angelman syndrome born to subfertile couples. J. Med. Genet. 42, 289–291.
CrossRef | PubMed |

MacLean, J. A. , and Wilkinson, M. F. (2005). Gene regulation in spermatogenesis. Curr. Top. Dev. Biol. ,in press.


Maher, E. R. , Brueton, L. A. , Bowdin, S. C. , Luharia, A. , and Cooper, W. , et al. (2003). Beckwith–Wiedemann syndrome and assisted reproduction technology (ART). J. Med. Genet. 40, 62–64.
CrossRef | PubMed |

Maitra, A. , Arking, D. E. , Shivapurkar, N. , Ikeda, M. , and Stastny, V. , et al. (2005). Genomic alterations in cultured human embryonic stem cells. Nat. Genet. ,in press.
PubMed |

Marques, C. J. , Carvalho, F. , Sousa, M. , and Barros, A. (2004). Genomic imprinting in disruptive spermatogenesis. Lancet 363, 1700–1702.
CrossRef | PubMed |

Mayer, W. , Niveleau, A. , Walter, J. , Fundele, R. , and Haaf, T. (2000). Demethylation of the zygotic paternal genome. Nature 403, 501–502.
PubMed |

Mertineit, C. , Yoder, J. A. , Taketo, T. , Laird, D. W. , Trasler, J. M. , and Bestor, T. H. (1998). Sex-specific exons control DNA methyltransferase in mammalian germ cells. Development 125, 889–897.
PubMed |

Moglabey, Y. B. , Kircheisen, R. , Seoud, M. , El Mogharbel, N. , Van den Veyrer, I. , and Slim, R. (1999). Genetic mapping of a maternal locus responsible for familial hydatidiform moles. Hum. Mol. Genet. 8, 667–671.
CrossRef | PubMed |

Monk, M. , Boubelik, M. , and Lehnert, S. (1987). Temporal and regional changes in DNA methylation in the embryonic, extraembryonic and germ-cell lineages during mouse embryo development. Development 99, 371–382.
PubMed |

Morgan, H. D. , Sutherland, H. G. , Martin, D. I. , and Whitelaw, E. (1999). Epigenetic inheritance at the agouti locus in the mouse. Nat. Genet. 23, 314–318.
CrossRef | PubMed |

Nikaido, I. , Saito, C. , Mizuno, Y. , Meguro, M. , and Bono, H. , et al. (2003). Discovery of imprinted transcripts in the mouse transcriptome using large-scale expression profiling. Genome Res. 13, 1402–1409.
CrossRef | PubMed |

Obata, Y. , and Kono, T. (2002). Maternal primary imprinting is established at a specific time for each gene throughout oocyte growth. J. Biol. Chem. 277, 5285–5289.
CrossRef | PubMed |

Okano, M. , Xie, S. , and Li, E. (1998). Cloning and characterization of a family of novel mammalian DNA (cytosine-5) methyltransferases. Nat. Genet. 19, 219–220.
CrossRef | PubMed |

Olek, A. , and Walter, J. (1997). The pre-implantation ontogeny of the H19 methylation imprint. Nat. Genet. 17, 275–276.
PubMed |

Orstavik, K. H. , Eiklid, K. , van der Hagen, C. B. , Spetalen, S. , Kierulf, K. , Skjeldal, O. , and Buiting, K. (2003). Another case of imprinting defect in a girl with Angelman syndrome who was conceived by intracytoplasmic semen injection. Am. J. Hum. Genet. 72, 218–219.
CrossRef | PubMed |

Oswald, J. , Engemann, S. , Lane, N. , Mayer, W. , Olek, A. , Fundele, R. , Dean, W. , Reik, W. , and Walter, J. (2000). Active demethylation of the paternal genome in the mouse zygote. Curr. Biol. 10, 475–478.
CrossRef | PubMed |

Ratnam, S. , Mertineit, C. , Ding, F. , Howell, C. Y. , Clarke, H. J. , Bestor, T. H. , Chaillet, J. R. , and Trasler, J. M. (2002). Dynamics of Dnmt1 methyltransferase expression and intracellular localization during oogenesis and preimplantation development. Dev. Biol. 245, 304–314.
CrossRef | PubMed |

Reik, W. , and Walter, J. (2001). Genomic imprinting: parental influence on the genome. Nat. Rev. Genet. 2, 21–32.
CrossRef | PubMed |

Rougier, N. , Bourc'his, D. , Gomes, D. M. , Niveleau, A. , Plachot, M. , Paldi, A. , and Viegas-Pequignot, E. (1998). Chromosome methylation patterns during mammalian preimplantation development. Genes Dev. 12, 2108–2113.
PubMed |

Rugg-Gunn, P. J. , Ferguson-Smith, A. C. , and Pedersen, R. A. (2005). Epigenetic status of human embryonic stem cells. Nat. Genet. 37, 585–587.
CrossRef | PubMed |

Sakai, Y. , Suetake, I. , Itoh, K. , Mizugaki, M. , Tajima, S. , and Yamashima, S. (2001). Expression of DNA methyltransferase (Dnmt1) in testicular germ cells during development of mouse embryo. Cell Struct. Funct. 26, 685–691.
CrossRef | PubMed |

Sakai, Y. , Suetake, I. , Shinozaki, F. , Yamashina, S. , and Tajima, S. (2004). Co-expression of de novo DNA methyltransferases Dnmt3a2 and Dnmt3L in gonocytes of mouse embryos. Gene Expr. Patterns 5, 231–237.
CrossRef | PubMed |

Santos, F. , and Dean, W. (2004). Epigenetic reprogramming during early development in mammals. Reproduction 127, 643–651.
CrossRef | PubMed |

Santos, F. , Hendrich, B. , Reik, W. , and Dean, W. (2002). Dynamic reprogramming of DNA methylation in the early mouse embryo. Dev. Biol. 241, 172–182.
CrossRef | PubMed |

Shamanski, F. L. , Kimura, Y. , Lavoir, M. C. , Pedersen, R. , and Yanagimachi, R. (1999). Status of genomic imprinting in mouse spermatids. Hum. Reprod. 14, 1050–1056.
CrossRef | PubMed |

Stoger, R. , Kubicka, P. , Liu, C. G. , Kafri, T. , Razin, A. , Cedar, H. , and Barlow, D. P. (1993). Maternal-specific methylation of the imprinted mouse Igf2r locus identifies the expressed locus as carrying the imprinting signal. Cell 73, 61–71.
CrossRef | PubMed |

Szabo, P. E. , Hubner, K. , Scholer, H. , and Mann, J. R. (2002). Allele-specific expression of imprinted genes in mouse migratory primordial germ cells. Mech. Dev. 115, 157–160.
CrossRef | PubMed |

Takada, S. , Paulsen, M. , Tevendale, M. , Tsai, C. E. , Kelsey, G. , Cattanach, B. M. , and Ferguson-Smith, A. C. (2002). Epigenetic analysis of the Dlk1-Gtl2 imprinted domain on mouse chromosome 12: implications for imprinting control from comparison with Igf2–H19. Hum. Mol. Genet. 11, 77–86.
CrossRef | PubMed |

Tremblay, K. D. , Duran, K. L. , and Bartolomei, M. S. (1997). A 5′ 2-kilobase-pair region of the imprinted mouse H19 gene exhibits exclusive paternal methylation throughout development. Mol. Cell. Biol. 17, 4322–4329.
PubMed |

Tycko, B. , and Morison, I. M. (2002). Physiological functions of imprinted genes. J. Cell. Physiol. 192, 245–258.
CrossRef | PubMed |

Ueda, T. , Yamazaki, K. , Suzuki, R. , Fujimoto, H. , Sasaki, H. , Sakaki, Y. , and Higashinakagawa, T. (1992). Parental methylation patterns of a transgenic locus in adult somatic tissues are imprinted during gametogenesis. Development 116, 831–839.
PubMed |

Ueda, T. , Abe, K. , Miura, A. , Yuzuriha, M. , and Zubair, M. , et al. (2000). The paternal methylation imprint of the mouse H19 locus is acquired in the gonocyte stage during foetal testis development. Genes Cells 5, 649–659.
CrossRef | PubMed |

Walsh, C. P. , Chaillet, J. R. , and Bestor, T. H. (1998). Transcription of IAP endogenous retroviruses is constrained by cytosine methylation. Nat. Genet. 20, 116–117.
CrossRef | PubMed |

Webster, K. E. , O'Bryan, M. K. , Fletcher, S. , Crewther, P. E. , and Aapola, U. , et al. (2005). Meiotic and epigenetic defects in Dnmt3L-knockout mouse spermatogenesis. Proc. Natl Acad. Sci. USA 102, 4068–4073.
CrossRef | PubMed |

Yamazaki, Y. , Mann, M. R. , Lee, S. S. , Marh, J. , McCarrey, J. R. , Yanagimachi, R. , and Bartolomei, M. S. (2003). Reprogramming of primordial germ cells begins before migration into the genital ridge, making these cells inadequate donors for reproductive cloning. Proc. Natl Acad. Sci. USA 100, 12 207–12 212.
CrossRef | PubMed |

Yoder, J. A. , and Bestor, T. H. (1998). A candidate mammalian DNA methyltransferase related to pmt1p of fission yeast. Hum. Mol. Genet. 7, 279–284.
CrossRef | PubMed |

Yoon, B. J. , Herman, H. , Sikora, A. , Smith, L. T. , Plass, C. , and Soloway, P. D. (2002). Regulation of DNA methylation of Rasgrf1. Nat. Genet. 30, 92–96.
CrossRef | PubMed |

Young, L. E. , Fernandes, K. , McEvoy, T. G. , Butterswith, S. C. , Gutierrez, C. G. , Carolan, C. , Broadbent, P. J. , Robinson, J. J. , Wilmut, I. , and Sinclair, K. D. (2001). Epigenetic change in IGF2R is associated with fetal overgrowth after sheep embryo culture. Nat. Genet. 27, 153–154.
CrossRef | PubMed |


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