Skip to main content

DNA Methyltransferases in Mammalian Oocytes

  • Chapter
  • First Online:
Oocytes

Part of the book series: Results and Problems in Cell Differentiation ((RESULTS,volume 63))

Abstract

Epigenetic mechanisms play important roles in properly occurring mammalian oogenesis. One of these mechanisms is DNA methylation adding a methyl group to the fifth carbon atom of the cytosine residues using S-adenosyl-l-methionine as a methyl donor. DNA methylation generally takes place at cytosine-phosphate-guanine (CpG) dinucleotide sites and rarely occurs at cytosine-phosphate-thymine (CpT), cytosine-phosphate-adenine (CpA), or cytosine-phosphate-cytosine sites, known as non-CpG sites. Basically, two different DNA methylation processes are identified: de novo methylation and maintenance methylation. While the de novo methylation functions in methylation of unmethylated DNA strands, maintenance methylation is capable of methylating hemi-methylated DNA strands following DNA replication. Both DNA methylation processes are catalyzed by special DNA methyltransferase (DNMT) enzymes. To date, five different DNMTs have been identified: DNMT1, DNMT3A, DNMT3B, DNMT3L, and DNMT2. In this chapter, we focus particularly on temporal and spatial expression of DNMTs in mammalian oocytes and granulosa cells.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 219.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 279.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 279.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Agarwal S, Rao A (1998) Modulation of chromatin structure regulates cytokine gene expression during T cell differentiation. Immunity 9(6):765–775

    Article  CAS  PubMed  Google Scholar 

  • Ambatipudi S, Cuenin C, Hernandez-Vargas H, Ghantous A, Le Calvez-Kelm F, Kaaks R, Barrdahl M, Boeing H, Aleksandrova K, Trichopoulou A, Lagiou P, Naska A, Palli D, Krogh V, Polidoro S, Tumino R, Panico S, Bueno-de-Mesquita B, Peeters PH, Quiros JR, Navarro C, Ardanaz E, Dorronsoro M, Key T, Vineis P, Murphy N, Riboli E, Romieu I, Herceg Z (2016) Tobacco smoking-associated genome-wide DNA methylation changes in the EPIC study. Epigenomics 8(5):599–618. doi:10.2217/epi-2016-0001

    Article  CAS  PubMed  Google Scholar 

  • Araujo FD, Croteau S, Slack AD, Milutinovic S, Bigey P, Price GB, Zannis-Hadjopoulos M, Szyf M (2001) The DNMT1 target recognition domain resides in the N terminus. J Biol Chem 276(10):6930–6936. doi:10.1074/jbc.M009037200

    Article  CAS  PubMed  Google Scholar 

  • Barlow DP, Bartolomei MS (2014) Genomic imprinting in mammals. Cold Spring Harb Perspect Biol 6(2). doi:10.1101/cshperspect.a018382

  • Bartolomei MS, Webber AL, Brunkow ME, Tilghman SM (1993) Epigenetic mechanisms underlying the imprinting of the mouse H19 gene. Genes Dev 7(9):1663–1673

    Article  CAS  PubMed  Google Scholar 

  • Bestor TH (2000) The DNA methyltransferases of mammals. Hum Mol Genet 9(16):2395–2402

    Article  CAS  PubMed  Google Scholar 

  • Bourc’his D, Bestor TH (2004) Meiotic catastrophe and retrotransposon reactivation in male germ cells lacking Dnmt3L. Nature 431(7004):96–99. doi:10.1038/nature02886

    Article  PubMed  Google Scholar 

  • Bourc’his D, Xu GL, Lin CS, Bollman B, Bestor TH (2001) Dnmt3L and the establishment of maternal genomic imprints. Science 294(5551):2536–2539. doi:10.1126/science.1065848

    Article  PubMed  Google Scholar 

  • Cedar H, Bergman Y (2012) Programming of DNA methylation patterns. Annu Rev Biochem 81:97–117. doi:10.1146/annurev-biochem-052610-091920

    Article  CAS  PubMed  Google Scholar 

  • Chedin F, Lieber MR, Hsieh CL (2002) The DNA methyltransferase-like protein DNMT3L stimulates de novo methylation by Dnmt3a. Proc Natl Acad Sci USA 99(26):16916–16921. doi:10.1073/pnas.262443999

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen T, Li E (2004) Structure and function of eukaryotic DNA methyltransferases. Curr Top Dev Biol 60:55–89. doi:10.1016/S0070-2153(04)60003-2

    Article  CAS  PubMed  Google Scholar 

  • Deshmukh RS, Ostrup O, Ostrup E, Vejlsted M, Niemann H, Lucas-Hahn A, Petersen B, Li J, Callesen H, Hyttel P (2011) DNA methylation in porcine preimplantation embryos developed in vivo and produced by in vitro fertilization, parthenogenetic activation and somatic cell nuclear transfer. Epigenetics 6(2):177–187

    Article  CAS  PubMed  Google Scholar 

  • Fang Y, Zhang X, Zhang J, Zhong R, Zhou D (2016) Global DNA methylation and related mRNA profiles in sheep oocytes and early embryos derived from pre-pubertal and adult donors. Anim Reprod Sci 164:144–151. doi:10.1016/j.anireprosci.2015.11.022

    Article  CAS  PubMed  Google Scholar 

  • Feinberg AP (2000) DNA methylation, genomic imprinting and cancer. Curr Top Microbiol Immunol 249:87–99

    CAS  PubMed  Google Scholar 

  • Feinberg AP, Cui H, Ohlsson R (2002) DNA methylation and genomic imprinting: insights from cancer into epigenetic mechanisms. Semin Cancer Biol 12(5):389–398

    Article  CAS  PubMed  Google Scholar 

  • Fernandez-Gonzalez R, Ramirez MA, Bilbao A, De Fonseca FR, Gutierrez-Adan A (2007) Suboptimal in vitro culture conditions: an epigenetic origin of long-term health effects. Mol Reprod Dev 74(9):1149–1156. doi:10.1002/mrd.20746

    Article  CAS  PubMed  Google Scholar 

  • Goll MG, Kirpekar F, Maggert KA, Yoder JA, Hsieh CL, Zhang X, Golic KG, Jacobsen SE, Bestor TH (2006) Methylation of tRNAAsp by the DNA methyltransferase homolog Dnmt2. Science 311(5759):395–398. doi:10.1126/science.1120976

    Article  CAS  PubMed  Google Scholar 

  • Goto H, Iwata H, Takeo S, Nisinosono K, Murakami S, Monji Y, Kuwayama T (2013) Effect of bovine age on the proliferative activity, global DNA methylation, relative telomere length and telomerase activity of granulosa cells. Zygote 21(3):256–264. doi:10.1017/S0967199411000499

    Article  CAS  PubMed  Google Scholar 

  • Gowher H, Liebert K, Hermann A, Xu G, Jeltsch A (2005) Mechanism of stimulation of catalytic activity of Dnmt3A and Dnmt3B DNA-(cytosine-C5)-methyltransferases by Dnmt3L. J Biol Chem 280(14):13341–13348. doi:10.1074/jbc.M413412200

    Article  CAS  PubMed  Google Scholar 

  • Hara S, Takano T, Fujikawa T, Yamada M, Wakai T, Kono T, Obata Y (2014) Forced expression of DNA methyltransferases during oocyte growth accelerates the establishment of methylation imprints but not functional genomic imprinting. Hum Mol Genet 23(14):3853–3864. doi:10.1093/hmg/ddu100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Heard E, Clerc P, Avner P (1997) X-chromosome inactivation in mammals. Annu Rev Genet 31:571–610. doi:10.1146/annurev.genet.31.1.571

    Article  CAS  PubMed  Google Scholar 

  • Henikoff S, Smith MM (2015) Histone variants and epigenetics. Cold Spring Harb Perspect Biol 7(1):a019364. doi:10.1101/cshperspect.a019364

    Article  PubMed  PubMed Central  Google Scholar 

  • Hirasawa R, Chiba H, Kaneda M, Tajima S, Li E, Jaenisch R, Sasaki H (2008) Maternal and zygotic Dnmt1 are necessary and sufficient for the maintenance of DNA methylation imprints during preimplantation development. Genes Dev 22(12):1607–1616. doi:10.1101/gad.1667008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huntriss J, Hinkins M, Oliver B, Harris SE, Beazley JC, Rutherford AJ, Gosden RG, Lanzendorf SE, Picton HM (2004) Expression of mRNAs for DNA methyltransferases and methyl-CpG-binding proteins in the human female germ line, preimplantation embryos, and embryonic stem cells. Mol Reprod Dev 67(3):323–336. doi:10.1002/mrd.20030

    Article  CAS  PubMed  Google Scholar 

  • Kageyama S, Liu H, Kaneko N, Ooga M, Nagata M, Aoki F (2007) Alterations in epigenetic modifications during oocyte growth in mice. Reproduction 133(1):85–94. doi:10.1530/REP-06-0025

    Article  CAS  PubMed  Google Scholar 

  • Kaneda M, Okano M, Hata K, Sado T, Tsujimoto N, Li E, Sasaki H (2004) Essential role for de novo DNA methyltransferase Dnmt3a in paternal and maternal imprinting. Nature 429(6994):900–903. doi:10.1038/nature02633

    Article  CAS  PubMed  Google Scholar 

  • Kato Y, Kaneda M, Hata K, Kumaki K, Hisano M, Kohara Y, Okano M, Li E, Nozaki M, Sasaki H (2007) Role of the Dnmt3 family in de novo methylation of imprinted and repetitive sequences during male germ cell development in the mouse. Hum Mol Genet 16(19):2272–2280. doi:10.1093/hmg/ddm179

    Article  CAS  PubMed  Google Scholar 

  • Ko YG, Nishino K, Hattori N, Arai Y, Tanaka S, Shiota K (2005) Stage-by-stage change in DNA methylation status of Dnmt1 locus during mouse early development. J Biol Chem 280(10):9627–9634. doi:10.1074/jbc.M413822200

    Article  CAS  PubMed  Google Scholar 

  • Kumar S, Cheng X, Klimasauskas S, Mi S, Posfai J, Roberts RJ, Wilson GG (1994) The DNA (cytosine-5) methyltransferases. Nucleic Acids Res 22(1):1–10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kurihara Y, Kawamura Y, Uchijima Y, Amamo T, Kobayashi H, Asano T, Kurihara H (2008) Maintenance of genomic methylation patterns during preimplantation development requires the somatic form of DNA methyltransferase 1. Dev Biol 313(1):335–346. doi:10.1016/j.ydbio.2007.10.033

    Article  CAS  PubMed  Google Scholar 

  • Law JA, Jacobsen SE (2010) Establishing, maintaining and modifying DNA methylation patterns in plants and animals. Nat Rev Genet 11(3):204–220. doi:10.1038/nrg2719

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liang XW, Cui XS, Sun SC, Jin YX, Heo YT, Namgoong S, Kim NH (2013) Superovulation induces defective methylation in line-1 retrotransposon elements in blastocyst. Reprod Biol Endocrinol 11:69. doi:10.1186/1477-7827-11-69

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liang Y, Fu XW, Li JJ, Yuan DS, Zhu SE (2014) DNA methylation pattern in mouse oocytes and their in vitro fertilized early embryos: effect of oocyte vitrification. Zygote 22(2):138–145. doi:10.1017/S0967199412000512

    Article  CAS  PubMed  Google Scholar 

  • Liu MH, Zhou WH, Chu DP, Fu L, Sha W, Li Y (2016) Ultrastructural changes and methylation of human oocytes vitrified at the germinal vesicle stage and matured in vitro after thawing. Gynecol Obstet Invest. doi:10.1159/000448143

  • Lodde V, Modina SC, Franciosi F, Zuccari E, Tessaro I, Luciano AM (2009a) Localization of DNA methyltransferase-1 during oocyte differentiation, in vitro maturation and early embryonic development in cow. Eur J Histochem 53(4):199–207

    Article  CAS  PubMed  Google Scholar 

  • Lodde V, Modina SC, Franciosi F, Zuccari E, Tessaro I, Luciano AM (2009b) Localization of DNA methyltransferase-1 during oocyte differentiation, in vitro maturation and early embryonic development in cow. Eur J Histochem 53(4):e24. doi:10.4081/ejh.2009.e24

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lorincz MC, Schubeler D, Hutchinson SR, Dickerson DR, Groudine M (2002) DNA methylation density influences the stability of an epigenetic imprint and Dnmt3a/b-independent de novo methylation. Mol Cell Biol 22(21):7572–7580

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ma JY, Li M, Ge ZJ, Luo Y, Ou XH, Song S, Tian D, Yang J, Zhang B, Ou-Yang YC, Hou Y, Liu Z, Schatten H, Sun QY (2012) Whole transcriptome analysis of the effects of type I diabetes on mouse oocytes. PLoS One 7(7):e41981. doi:10.1371/journal.pone.0041981

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ma P, de Waal E, Weaver JR, Bartolomei MS, Schultz RM (2015) A DNMT3A2-HDAC2 complex is essential for genomic imprinting and genome integrity in mouse oocytes. Cell Rep 13(8):1552–1560. doi:10.1016/j.celrep.2015.10.031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mertineit C, Yoder JA, Taketo T, Laird DW, Trasler JM, Bestor TH (1998) Sex-specific exons control DNA methyltransferase in mammalian germ cells. Development 125(5):889–897

    CAS  PubMed  Google Scholar 

  • Neri F, Krepelova A, Incarnato D, Maldotti M, Parlato C, Galvagni F, Matarese F, Stunnenberg HG, Oliviero S (2013) Dnmt3L antagonizes DNA methylation at bivalent promoters and favors DNA methylation at gene bodies in ESCs. Cell 155(1):121–134. doi:10.1016/j.cell.2013.08.056

    Article  CAS  PubMed  Google Scholar 

  • O’Doherty AM, O’Shea LC, Fair T (2012) Bovine DNA methylation imprints are established in an oocyte size-specific manner, which are coordinated with the expression of the DNMT3 family proteins. Biol Reprod 86(3):67. doi:10.1095/biolreprod.111.094946

    PubMed  Google Scholar 

  • Okano M, Xie S, Li E (1998a) Cloning and characterization of a family of novel mammalian DNA (cytosine-5) methyltransferases. Nat Genet 19(3):219–220. doi:10.1038/890

    Article  CAS  PubMed  Google Scholar 

  • Okano M, Xie S, Li E (1998b) Dnmt2 is not required for de novo and maintenance methylation of viral DNA in embryonic stem cells. Nucleic Acids Res 26(11):2536–2540

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Okano M, Bell DW, Haber DA, Li E (1999) DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 99(3):247–257

    Article  CAS  PubMed  Google Scholar 

  • Ostler KR, Davis EM, Payne SL, Gosalia BB, Exposito-Cespedes J, Le Beau MM, Godley LA (2007) Cancer cells express aberrant DNMT3B transcripts encoding truncated proteins. Oncogene 26(38):5553–5563. doi:10.1038/sj.onc.1210351

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Petrussa L, Van de Velde H, De Rycke M (2014) Dynamic regulation of DNA methyltransferases in human oocytes and preimplantation embryos after assisted reproductive technologies. Mol Hum Reprod 20(9):861–874. doi:10.1093/molehr/gau049

    Article  CAS  PubMed  Google Scholar 

  • Portela A, Esteller M (2010) Epigenetic modifications and human disease. Nat Biotechnol 28(10):1057–1068. doi:10.1038/nbt.1685

    Article  CAS  PubMed  Google Scholar 

  • Posfai J, Bhagwat AS, Posfai G, Roberts RJ (1989) Predictive motifs derived from cytosine methyltransferases. Nucleic Acids Res 17(7):2421–2435

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pradhan S, Bacolla A, Wells RD, Roberts RJ (1999) Recombinant human DNA (cytosine-5) methyltransferase. I. Expression, purification, and comparison of de novo and maintenance methylation. J Biol Chem 274(46):33002–33010

    Article  CAS  PubMed  Google Scholar 

  • 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 245(2):304–314. doi:10.1006/dbio.2002.0628

    Article  CAS  PubMed  Google Scholar 

  • Reik W, Dean W (2001) DNA methylation and mammalian epigenetics. Electrophoresis 22(14):2838–2843. doi:10.1002/1522-2683

    Article  CAS  PubMed  Google Scholar 

  • Richardson B (2003) Impact of aging on DNA methylation. Ageing Res Rev 2(3):245–261

    Article  CAS  PubMed  Google Scholar 

  • Robertson KD, Wolffe AP (2000) DNA methylation in health and disease. Nat Rev Genet 1(1):11–19. doi:10.1038/35049533

    Article  CAS  PubMed  Google Scholar 

  • Song Z, Min L, Pan Q, Shi Q, Shen W (2009) Maternal imprinting during mouse oocyte growth in vivo and in vitro. Biochem Biophys Res Commun 387(4):800–805. doi:10.1016/j.bbrc.2009.07.131

    Article  CAS  PubMed  Google Scholar 

  • Stoger R, Kubicka P, Liu CG, Kafri T, Razin A, Cedar H, Barlow DP (1993) Maternal-specific methylation of the imprinted mouse Igf2r locus identifies the expressed locus as carrying the imprinting signal. Cell 73(1):61–71

    Article  CAS  PubMed  Google Scholar 

  • Turek-Plewa J, Jagodzinski PP (2005) The role of mammalian DNA methyltransferases in the regulation of gene expression. Cell Mol Biol Lett 10(4):631–647

    CAS  PubMed  Google Scholar 

  • Uysal F, Akkoyunlu G, Ozturk S (2015) Dynamic expression of DNA methyltransferases (DNMTs) in oocytes and early embryos. Biochimie 116:103–113. doi:10.1016/j.biochi.2015.06.019

    Article  CAS  PubMed  Google Scholar 

  • Uysal F, Akkoyunlu G, Ozturk S (2016) DNA methyltransferases exhibit dynamic expression during spermatogenesis. Reprod Biomed Online 33(6):690–702. doi:10.1016/j.rbmo.2016.08.022

    Article  CAS  PubMed  Google Scholar 

  • Vassena R, Dee Schramm R, Latham KE (2005) Species-dependent expression patterns of DNA methyltransferase genes in mammalian oocytes and preimplantation embryos. Mol Reprod Dev 72(4):430–436. doi:10.1002/mrd.20375

    Article  CAS  PubMed  Google Scholar 

  • Verlhac MH, Terret ME (2016) Oocyte maturation and development. F1000Res 5. doi:10.12688/f1000research.7892.1

  • Virani S, Rentschler KM, Nishijo M, Ruangyuttikarn W, Swaddiwudhipong W, Basu N, Rozek LS (2016) DNA methylation is differentially associated with environmental cadmium exposure based on sex and smoking status. Chemosphere 145:284–290. doi:10.1016/j.chemosphere.2015.10.123

    Article  CAS  PubMed  Google Scholar 

  • Watanabe D, Suetake I, Tada T, Tajima S (2002) Stage- and cell-specific expression of Dnmt3a and Dnmt3b during embryogenesis. Mech Dev 118(1–2):187–190

    Article  CAS  PubMed  Google Scholar 

  • Wei Y, Huan Y, Shi Y, Liu Z, Bou G, Luo Y, Zhang L, Yang C, Kong Q, Tian J, Xia P, Sun QY, Liu Z (2011) Unfaithful maintenance of methylation imprints due to loss of maternal nuclear Dnmt1 during somatic cell nuclear transfer. PLoS One 6(5):e20154. doi:10.1371/journal.pone.0020154

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Whidden L, Martel J, Rahimi S, Richard Chaillet J, Chan D, Trasler JM (2016) Compromised oocyte quality and assisted reproduction contribute to sex-specific effects on offspring outcomes and epigenetic patterning. Hum Mol Genet. doi:10.1093/hmg/ddw293

  • Yan J, Zhang L, Wang T, Li R, Liu P, Yan L, Qiao J (2014) Effect of vitrification at the germinal vesicle stage on the global methylation status in mouse oocytes subsequently matured in vitro. Chin Med J 127(23):4019–4024

    PubMed  Google Scholar 

  • Yang X, Smith SL, Tian XC, Lewin HA, Renard JP, Wakayama T (2007) Nuclear reprogramming of cloned embryos and its implications for therapeutic cloning. Nat Genet 39(3):295–302. doi:10.1038/ng1973

    Article  CAS  PubMed  Google Scholar 

  • Yoder JA, Soman NS, Verdine GL, Bestor TH (1997) DNA (cytosine-5)-methyltransferases in mouse cells and tissues. Studies with a mechanism-based probe. J Mol Biol 270(3):385–395. doi:10.1006/jmbi.1997.1125

    Article  CAS  PubMed  Google Scholar 

  • Yu B, Russanova VR, Gravina S, Hartley S, Mullikin JC, Ignezweski A, Graham J, Segars JH, DeCherney AH, Howard BH (2015) DNA methylome and transcriptome sequencing in human ovarian granulosa cells links age-related changes in gene expression to gene body methylation and 3′-end GC density. Oncotarget 6(6):3627–3643. doi:10.18632/oncotarget.2875

    Article  PubMed  PubMed Central  Google Scholar 

  • Yue MX, Fu XW, Zhou GB, Hou YP, Du M, Wang L, Zhu SE (2012) Abnormal DNA methylation in oocytes could be associated with a decrease in reproductive potential in old mice. J Assist Reprod Genet 29(7):643–650. doi:10.1007/s10815-012-9780-4

    Article  PubMed  PubMed Central  Google Scholar 

  • Zaitseva I, Zaitsev S, Alenina N, Bader M, Krivokharchenko A (2007) Dynamics of DNA-demethylation in early mouse and rat embryos developed in vivo and in vitro. Mol Reprod Dev 74(10):1255–1261. doi:10.1002/mrd.20704

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Saffet Ozturk .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Uysal, F., Ozturk, S. (2017). DNA Methyltransferases in Mammalian Oocytes. In: Kloc, M. (eds) Oocytes. Results and Problems in Cell Differentiation, vol 63. Springer, Cham. https://doi.org/10.1007/978-3-319-60855-6_10

Download citation

Publish with us

Policies and ethics