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Regulated Synthesis and Role of DNA Methyltransferase During Meiosis

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Germ Cell Development, Division, Disruption and Death

Part of the book series: Serono Symposia USA Norwell, Massachusetts ((SERONOSYMP))

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Abstract

In mammals, the methylation of cytosine residues in DNA is postulated to be involved in a number of processes including gene regulation, development, X-chromosome inactivation, genomic imprinting, and carcinogenesis. Sex- and sequence-specific patterns of DNA methylation are established in the germ line (1–3) and further modified during embryogenesis. The chemical modification of genes by DNA methylation provides a way in which genes can be turned on or off at specific times. Overall, the sperm genome is more methylated than that of the oocyte (4). Methylation of DNA is one of the major candidates proposed to mark the mother’s and father’s genes differently, in the process of genomic imprinting, which is also initiated in the germ line (5, 6). Our objectives are to determine the mechanisms by which DNA methylation patterns are established during spermatogenesis and the impact on the early embryo of disrupting DNA methylation in male germ cells. Our results to date indicate that DNA methylation is highly regulated in the germ line (1, 7–10) and suggest that decreases in DNA methylation in male germ cells result in alterations in sperm production and abnormalities in early embryo development (11).

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References

  1. Trasler JM. Hake LE, Johnson PA, Alcivar AA, Millette CF, Hecht NB. DNA methylation and demethylation events during meiotic prophase in the mouse testis. Mol Cell Biol 1990;10:1828–34.

    PubMed  CAS  Google Scholar 

  2. Chaillet JR, Vogt TF, Beier DR, Leder P. Parental-specific methylation of an imprinted transgene is established during gametogenesis and progressively changes during embryogenesis. Cell 1991;66:77–83.

    Article  PubMed  CAS  Google Scholar 

  3. Kafri T, Ariel M, Brandeis M, Shemer R, Urven L, McCarrey J, et al. Developmental pattern of gene-specific DNA methylation in the mouse embryo and germ line. Genes Dev 1992;6:705–14.

    Article  PubMed  CAS  Google Scholar 

  4. Monk M, Boubelik M, Lehnert S. Temporal and regional changes in DNA methylation in the embryonic, extraembryonic and germ cell lineages during mouse embryo development. Development (Camb) 1987;99:371–82.

    CAS  Google Scholar 

  5. Meehan R, Lewis J, Cross S, Nan X, Jeppesen P, Bird A. Transcriptional repression by methylation of CpG. J Cell Sci Suppl 1992;16:9–14.

    PubMed  CAS  Google Scholar 

  6. Barlow DP. Methylation and imprinting: from host defense to gene regulation? Science 1993;260:309–10.

    Article  PubMed  CAS  Google Scholar 

  7. Benoit G, Trasler JM. Developmental expression of DNA methyltransferase messenger ribonucleic acid, protein and enzyme activity in the mouse testis. Biol Reprod 1994;50:1312–9.

    Article  PubMed  CAS  Google Scholar 

  8. Jue K, Benoit G, Alcivar AA, Trasler JM. Developmental and hormonal regulation of DNA methyltransferase in the rat testis. Biol Reprod 1995;52:1364–71.

    Article  PubMed  CAS  Google Scholar 

  9. Jue K, Bestor TH, Trasler JM. Regulated synthesis and localization of DNA methyltransferase during spermatogenesis. Biol Reprod 1995;53:561–9.

    Google Scholar 

  10. Trasler JM, Alcivar AA, Hake LE, Bestor T, Hecht NB. DNA methyltransferase is developmentally expressed in replicating and non-replicating male germ cells. Nucleic Acids Res 1992;20:2541–5.

    Article  PubMed  CAS  Google Scholar 

  11. Doerksen T, Trasler JM. Developmental exposure of male germ cells to 5-azacytidine results in abnormal preimplantation development in rats. Biol Reprod 1996;55:1155–62.

    Article  PubMed  CAS  Google Scholar 

  12. Bestor TH, Tycko B. Creation of genomic methylation patterns. Nat Genet 1996; 12:363–6.

    Article  PubMed  CAS  Google Scholar 

  13. Iguchi-Ariga SMM, Schaffner W. CpG methylation of the cAMP responsive enhancer/ promoter TGACGTCA abolishes specific factor binding as well as transcriptional activation. Genes Dev 1989;3:612–9.

    Article  PubMed  CAS  Google Scholar 

  14. Pfeifer G, Steigerwald S, Hansen RS, Gartier SM, Riggs AD. Polymerase-chain reaction aided genomic sequencing of an X chromosome linked CpG island: methylation patterns suggest clonal inheritance, CpG site autonomy, and an explanation of activity state stability. Proc Natl Acad Sci USA 1990;87:8252–6.

    Article  PubMed  CAS  Google Scholar 

  15. Li E, Bestor TH, Jaenisch R. Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell 1992;69:915–26.

    Article  PubMed  CAS  Google Scholar 

  16. Lei H, Oh SP, Okano M, Juttennann R, Goss KA, Jaenisch R, et al. De novo DNA cytosine methyltransferase activities in mouse embryonic stem cells. Development (Camb) 1996;122:3195–205.

    CAS  Google Scholar 

  17. Trasler JM, Trasler DG, Bestor T, Li E, Ghibu F. DNA methyltransferase in normal and Dnmtn/Dnmtn mouse embryos. Dev Dyn 1996;206:239–47.

    Article  PubMed  CAS  Google Scholar 

  18. Beard C, Li E, Jaenisch R. Loss of methylation activates Xist in somatic but not in embryonic cells. Genes Dev 1995;9:2325–34.

    Article  PubMed  CAS  Google Scholar 

  19. Li E, Beard C, Jaenisch R. Role for DNA methylation in genomic imprinting. Nature (Lond) 1993;366:362–5.

    Article  CAS  Google Scholar 

  20. Tucker KL, Beard C, Dausman J, Jackson-Grusby L, Laird PW, Lei H, et al. Germ-line passage is required for establishment of methylation and expression patterns of imprinted but not nonimprinted genes. Genes Dev 1996;10:1008–20.

    Article  PubMed  CAS  Google Scholar 

  21. Bestor TH, Coxon A. The pros and cons of DNA methylation. Curr Biol 1993;3: 384–6.

    Article  PubMed  CAS  Google Scholar 

  22. Jones PA. DNA methylation errors and cancer. Cancer Res 1996;56:2463–7.

    PubMed  CAS  Google Scholar 

  23. Laird PW, Jaenisch R. DNA methylation and cancer. Hum Mol Genet 1994;3:1487–95.

    PubMed  CAS  Google Scholar 

  24. Bestor T, Laudano A, Mattaliano R, Ingram V. Cloning and sequencing of a cDNA encoding DNA methyltransferase of mouse cells. J Mol Biol 1988;203:971–83.

    Article  PubMed  CAS  Google Scholar 

  25. Yen R-W, Vertino PM, Nelkin BD, Yu JJ, El-Deiry W, Cumaraswarny A, et al. Isolation and characterization of the cDNA encoding human DNA methyltransferase. Nucleic Acids Res 1992;9:2287–91.

    Article  Google Scholar 

  26. Bestor TH. Activation of mammalian DNA methyltransferase by cleavage of a Znbinding regulatory domain. EMBO J 1992; 11:2611–8.

    PubMed  CAS  Google Scholar 

  27. Bestor TH, Ingram VM. Two DNA methyltransferases from murine erythroleukemia cells: purification, sequence specificity, and mode of interaction with DNA. Proc Natl Acad Sci USA 1983:80:5559–63.

    Article  PubMed  CAS  Google Scholar 

  28. Singer-Sam J, Robinson MO, Bellvé AR, Simon MI, Riggs AD. Measurement by quantitative PCR of changes in HPRT, PGK-1, PGK-2, APRT, MTase, and Zfy gene transcripts during mouse spennatogenesis. Nucleic Acids Res 1990;18:1255–9.

    Article  PubMed  CAS  Google Scholar 

  29. Numata M, Ono T, Iseki S. Expression and localization of the mRNA for DNA (cytosine-5)-methyltransferase in mouse seminiferous tubules. J Histochem Cytochem 1994;42:1271–6.

    Article  PubMed  CAS  Google Scholar 

  30. Leonhardt HL, Page AW, Weier H-U, Bestor TH. A targeting sequence directs DNA methyltransferase to sites of DNA replication in mammalian nuclei. Cell 1992;71:865–73.

    Article  PubMed  CAS  Google Scholar 

  31. Carlson LL, Page AW, Bestor TH. Subcellular localization and properties of DNA methyltransferase in preimplantation mouse embryos: implications for genomic imprinting. Genes Devel 1992;6:2536–41.

    Article  PubMed  CAS  Google Scholar 

  32. Tucker KL, Talbot D, Lee MA, Leonhardt H, Jaenisch R. Complementation of methylation deficiency in embryonic stem cells by a DNA methyltransferase minigene. Proc Natl Acad Sci USA 1996;93:12920–5.

    Article  PubMed  CAS  Google Scholar 

  33. Yoder J, Yen R-W, Vertino PM, Bestor TH, Baylin SB. New 5′ regions of the murine and human genes for DNA (cytosine-5)-methyltransferase. J Biol Chem 1996;271: 31092–7.

    Article  PubMed  CAS  Google Scholar 

  34. Jones PA, Taylor SM. Cellular differentiation, cytidine analogues, and DNA methylation. Cell 1980;20:85–93.

    Article  PubMed  CAS  Google Scholar 

  35. Gabbara S, Bhagwat AS. The mechanism of inhibition of DNA (cytosine-5-)-methyltransferases by 5-azacytosine is likely to involve methyl transfer to the inhibitor. Biochem J 1995;307:87–92.

    PubMed  CAS  Google Scholar 

  36. Juttermann R, Li E, Jaenisch R. Toxicity of 5-aza-2′-deoxycytidine to mammalian cells is mediated primarily by covalent trapping of DNA methyltransferase rather than DNA demethylation. Proc Natl Acad Sci USA 1994;91:11797–801.

    Article  PubMed  CAS  Google Scholar 

  37. Jones PA. Altering gene expression with 5-azacytidine. Cell 1985;40:485–6.

    Article  PubMed  CAS  Google Scholar 

  38. Jones PA, Taylor SM, Mohandas T, Shapiro LJ. Cell cycle-specific reactivation of an inactive X-chromosome locus by 5-azadeoxycytidine. Proc Natl Acad Sci USA 1982;79:1215–9.

    Article  PubMed  CAS  Google Scholar 

  39. Ley TJ, DeSimone J, Anagnou NP, Keller GH, Humphries RK, Turner PH, et al. 5-Azacytidine selectively increases τ-globin synthesis in a patient with β+ thalassemia. N Engl J Med 1982:307:1469–75.

    Article  PubMed  CAS  Google Scholar 

  40. Constantinides PG, Jones PA, Gevers W. Functional striated muscle cells from non-myoblast precursors following 5-azacytidine treatment. Nature (Lond) 1977;267: 364–6.

    Article  CAS  Google Scholar 

  41. Carr BI, Rahbar S, Asmeron Y, Riggs A, Winberg CD. Carcinogenicity and haemoglobin synthesis induction by cytidine analogues. Br J Cancer 1988;57:395–402.

    Article  PubMed  CAS  Google Scholar 

  42. Carr BI, Reilly JG, Smith SS, Winberg C, Riggs A. The tumorigenicity of 5-azacytidine in the male Fischerrat. Carcinogenesis 1984;5:1583–90.

    Article  PubMed  CAS  Google Scholar 

  43. Clermont Y. Kinetics of spermatogenesis in mammals: seminiferous epithelium cycle and spermatogonial renewal. Physiol Rev 1972;52:198–236.

    PubMed  CAS  Google Scholar 

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Authors
  1. Jacquetta M. Trasler
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  2. Carmen Mertineit
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  3. Tonia E. Doerksen
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Editor information

Editors and Affiliations

  1. Division of Reproductive Biology Department of Population Dynamics School of Hygiene and Public Health, Johns Hopkins University, Baltimore, MD, 21205, USA

    Barry R. Zirkin Ph.D.

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© 1998 Springer-Verlag New York, Inc.

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Trasler, J.M., Mertineit, C., Doerksen, T.E. (1998). Regulated Synthesis and Role of DNA Methyltransferase During Meiosis. In: Zirkin, B.R. (eds) Germ Cell Development, Division, Disruption and Death. Serono Symposia USA Norwell, Massachusetts. Springer, New York, NY. https://doi.org/10.1007/978-1-4612-2206-4_8

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  • DOI: https://doi.org/10.1007/978-1-4612-2206-4_8

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4612-7458-2

  • Online ISBN: 978-1-4612-2206-4

  • eBook Packages: Springer Book Archive

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