Abstract
DNA methylation is one of the epigenetic mechanisms and plays important roles during oogenesis and early embryo development in mammals. DNA methylation is basically known as adding a methyl group to the fifth carbon atom of cytosine residues within cytosine–phosphate–guanine (CpG) and non-CpG dinucleotide sites. This mechanism is composed of two main processes: de novo methylation and maintenance methylation, both of which are catalyzed by specific DNA methyltransferase (DNMT) enzymes. To date, six different DNMTs have been characterized in mammals defined as DNMT1, DNMT2, DNMT3A, DNMT3B, DNMT3C, and DNMT3L. While DNMT1 primarily functions in maintenance methylation, both DNMT3A and DNMT3B are essentially responsible for de novo methylation. As is known, either maintenance or de novo methylation processes appears during oocyte and early embryo development terms. The aim of the present study is to investigate spatial and temporal expression levels and subcellular localizations of the DNMT1, DNMT3A, and DNMT3B proteins in the mouse germinal vesicle (GV) and metaphase II (MII) oocytes, and early embryos from 1-cell to blastocyst stages. We found that there are remarkable differences in the expressional levels and subcellular localizations of the DNMT1, DNMT3A and DNMT3B proteins in the GV and MII oocytes, and 1-cell, 2-cell, 4-cell, 8-cell, morula, and blastocyst stage embryos. The fluctuations in the expression of DNMT proteins in the analyzed oocytes and early embryos are largely compatible with DNA methylation changes and genomic imprintestablishment appearing during oogenesis and early embryo development. To understand precisemolecular biological meaning of differently expressing DNMTs in the early developmental periods, further studies are required.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Akkoyunlu G, Ustunel I, Demir R (2007) The distribution of transglutaminase in the rat oocytes and embryos. Theriogenology 68(6):834–841
Albert M, Peters AH (2009) Genetic and epigenetic control of early mouse development. Curr Opin Genet Dev 19(2):113–121
Barau J, Teissandier A, Zamudio N, Roy S, Nalesso V, Herault Y, Guillou F, Bourc’his D (2016) The DNA methyltransferase DNMT3C protects male germ cells from transposon activity. Science 354(6314):909–912
Bartolomei MS, Ferguson-Smith AC (2011) Mammalian genomic imprinting. Cold Spring Harb Perspect Biol 3(7)
Bestor TH (2000) The DNA methyltransferases of mammals. Hum Mol Genet 9(16):2395–2402
Bolton VN, Oades PJ, Johnson MH (1984) The relationship between cleavage, DNA replication, and gene expression in the mouse 2-cell embryo. J Embryol Exp Morphol 79:139–163
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
Deplus R, Brenner C, Burgers WA, Putmans P, Kouzarides T, de Launoit Y, Fuks F (2002) Dnmt3L is a transcriptional repressor that recruits histone deacetylase. Nucleic Acids Res 30(17):3831–3838
Dobbs KB, Rodriguez M, Sudano MJ, Ortega MS, Hansen PJ (2013) Dynamics of DNA methylation during early development of the preimplantation bovine embryo. PLoS ONE 8(6):e66230
Fatemi M, Hermann A, Gowher H, Jeltsch A (2002) Dnmt3a and Dnmt1 functionally cooperate during de novo methylation of DNA. Eur J Biochem 269(20):4981–4984
Fujimori T (2010) Preimplantation development of mouse: a view from cellular behavior. Dev Growth Differ 52(3):253–262
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
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
Howell CY, Bestor TH, Ding F, Latham KE, Mertineit C, Trasler JM, Chaillet JR (2001) Genomic imprinting disrupted by a maternal effect mutation in the Dnmt1 gene. Cell 104(6):829–838
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
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
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
Lodde V, Modina SC, Franciosi F, Zuccari E, Tessaro I, Luciano AM (2009) Localization of DNA methyltransferase-1 during oocyte differentiation, in vitro maturation and early embryonic development in cow. Eur J Histochem 53(4):199–207
Margot JB, Ehrenhofer-Murray AE, Leonhardt H (2003) Interactions within the mammalian DNA methyltransferase family. BMC Mol Biol 4:7
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
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
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
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
Saitou M, Kagiwada S, Kurimoto K (2012) Epigenetic reprogramming in mouse pre-implantation development and primordial germ cells. Development 139(1):15–31
Smallwood SA, Kelsey G (2012) De novo DNA methylation: a germ cell perspective. Trends Genet 28(1):33–42
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
Uysal F, Akkoyunlu G, Ozturk S (2015) Dynamic expression of DNA methyltransferases (DNMTs) in oocytes and early embryos. Biochimie 116:103–113
Verlhac MH, Terret ME (2016) Oocyte Maturation and Development. F1000Res 5
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
Zhang Y, Yang Z, Wu J (2007) Signaling pathways and preimplantation development of mammalian embryos. FEBS J 274(17):4349–4359
Funding
This study was supported by Akdeniz University Scientific Research Projects Coordination Unit (Project Number: 2014.02.0122.013).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that there is no conflict of interest.
Rights and permissions
About this article
Cite this article
Uysal, F., Ozturk, S. & Akkoyunlu, G. DNMT1, DNMT3A and DNMT3B proteins are differently expressed in mouse oocytes and early embryos. J Mol Hist 48, 417–426 (2017). https://doi.org/10.1007/s10735-017-9739-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10735-017-9739-y