Animal Reproduction (AR)
https://animal-reproduction.org/article/doi/10.21451/1984-3143-AR2018-0087
Animal Reproduction (AR)
Original Articles

The effects of biological aging on global DNA methylation, histone modification, and epigenetic modifiers in the mouse germinal vesicle stage oocyte

Kira Lynn Marshall, Juanbin Wang, Tieming Ji, Rocío Melissa Rivera

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Abstract

A cultural trend in developed countries is favoring a delay in maternal age at first childbirth. In mammals fertility and chronological age show an inverse correlation. Oocyte quality is a contributing factor to this multifactorial phenomenon that may be influenced by age-related changes in the oocyte epigenome. Based on previous reports, we hypothesized that advanced maternal age would lead to alterations in the oocyte’s epigenome. We tested our hypothesis by determining protein levels of various epigenetic modifications and modifiers in fully-grown (³70 µm), germinal vesicle (GV) stage oocytes of young (10-13 weeks) and aged (69-70 weeks) mice. Our results demonstrate a significant increase in protein amounts of the maintenance DNA methyltransferase DNMT1 (P = 0.003) and a trend toward increased global DNA methylation (P = 0.09) with advanced age. MeCP2, a methyl DNA binding domain protein, recognizes methylated DNA and induces chromatin compaction and silencing. We hypothesized that chromatin associated MeCP2 would be increased similarly to DNA methylation in oocytes of aged female mice. However, we detected a significant decrease (P = 0.0013) in protein abundance of MeCP2 between GV stage oocytes from young and aged females. Histone posttranslational modifications can also alter chromatin conformation. Di-methylation of H3K9 (H3K9me2) is associated with permissive heterochromatin while acetylation of H4K5 (H4K5ac) is associated with euchromatin. Our results indicate a trend toward decreasing H3K9me2 (P = 0.077) with advanced female age and no significant differences in levels of H4K5ac. These data demonstrate that physiologic aging affects the mouse oocyte epigenome and provide a better understanding of the mechanisms underlying the decrease in oocyte quality and reproductive potential of aged females.

Keywords

epigenome, Histone acetylation, Histone methylation, Methyl DNA binding domain proteins, DNA methyltransferase.

References

Adenot PG, Mercier Y, Renard JP, Thompson EM. 1997. Differential H4 acetylation of paternal and maternal chromatin precedes DNA replication and differential transcriptional activity in pronuclei of 1-cell mouse embryos. Development, 124:4615-4625.

Akiyama T, Nagata M, Aoki F. 2006. Inadequate histone deacetylation during oocyte meiosis causes aneuploidy and embryo death in mice. Proc Natl Acad Sci U S A, 103:7339-7344.

Allfrey VG, Faulkner R, Mirsky AE. 1964. Acetylation and methylation of histones and their possible role in the regulation of RNA synthesis. Proc Natl Acad Sci U S A, 51:786-794.

Almamun M, 2011. Size-dependent acquisition of global DNA methylation in oocytes is altered by hormonal stimulation. Thesis Master of Science. Faculty of the Graduate School University of Missouri, Columbia, MO, EUA.

Arney KL, Bao S, Bannister AJ, Kouzarides T, Surani MA. 2002. Histone methylation defines epigenetic asymmetry in the mouse zygote. Int J Dev Biol, 46:317-320.

Bannister AJ, Schneider R, Myers FA, Thorne AW, Crane-Robinson C, Kouzarides T. 2005. Spatial distribution of di- and tri-methyl lysine 36 of histone H3 at active genes. J Biol Chem, 280:17732-17736.

Barton SC, Arney KL, Shi W, Niveleau A, Fundele R, Surani MA, Haaf T. 2001. Genome-wide methylation patterns in normal and uniparental early mouse embryos. Hum Mol Genet, 10:2983-2987.

Baubec T, Ivanek R, Lienert F, Schubeler D. 2013. Methylation-dependent and -independent genomic targeting principles of the MBD protein family. Cell, 153:480-492.

Beaujean N. 2014. Histone post-translational modifications in preimplantation mouse embryos and their role in nuclear architecture. Mol Reprod Dev, 81:100-112.

Bernstein BE, Kamal M, Lindblad-Toh K, Bekiranov S, Bailey DK, Huebert DJ, McMahon S, Karlsson EK, Kulbokas EJ, 3rd, Gingeras TR, Schreiber SL, Lander ES. 2005. Genomic maps and comparative analysis of histone modifications in human and mouse. Cell, 120:169-181.

Bestor TH. 2000. The DNA methyltransferases of mammals. Hum Mol Genet, 9:2395-2402.

Biniszkiewicz D, Gribnau J, Ramsahoye B, Gaudet F, Eggan K, Humpherys D, Mastrangelo MA, Jun Z, Walter J, Jaenisch R. 2002. Dnmt1 overexpression causes genomic hypermethylation, loss of imprinting, and embryonic lethality. Mol Cell Biol, 22:2124-2135.

Bouniol-Baly C, Hamraoui L, Guibert J, Beaujean N, Szollosi MS, Debey P. 1999. Differential transcriptional activity associated with chromatin configuration in fully grown mouse germinal vesicle oocytes. Biol Reprod, 60:580-587.

Boyes J, Bird A. 1991. DNA methylation inhibits transcription indirectly via a methyl-CpG binding protein. Cell, 64:1123-1134.

Brenet F, Moh M, Funk P, Feierstein E, Viale AJ, Socci ND, Scandura JM. 2011. DNA methylation of the first exon is tightly linked to transcriptional silencing. PloS one, 6:e14524.

Broekmans FJ, Soules MR, Fauser BC. 2009. Ovarian aging: mechanisms and clinical consequences. Endocr Rev, 30:465-493.

Brownell JE, Zhou J, Ranalli T, Kobayashi R, Edmondson DG, Roth SY, Allis CD. 1996. Tetrahymena histone acetyltransferase A: a homolog to yeast Gcn5p linking histone acetylation to gene activation. Cell, 84:843-851.

Carlson LL, Page AW, Bestor TH. 1992. Properties and localization of DNA methyltransferase in preimplantation mouse embryos: implications for genomic imprinting. Genes Dev, 6:2536-2541.

Choy JS, Wei S, Lee JY, Tan S, Chu S, Lee TH. 2010. DNA methylation increases nucleosome compaction and rigidity. J Am Chem Soc, 132:1782-1783.

Cirio MC, Ratnam S, Ding F, Reinhart B, Navara C, Chaillet JR. 2008. Preimplantation expression of the somatic form of Dnmt1 suggests a role in the inheritance of genomic imprints. BMC Dev Biol, 8:9. Doi: 10.1186/1471-213X-8-9.

Cohen MA, Lindheim SR, Sauer MV. 1999. Donor age is paramount to success in oocyte donation. Hum Reprod, 14:2755-2758.

Danilovich N, Ram Sairam M. 2006. Recent female mouse models displaying advanced reproductive aging. Exp Gerontol, 41:117-122.

DeLange RJ, Hooper JA, Smith EL. 1972. Complete amino-acid sequence of calf-thymus histone 3. Proc Natl Acad Sci U S A, 69:882-884.

DeLange RJ, Smith EL. 1973. Histone 3. I. Isolation and sequences of the tryptic peptides from the maleylated calf thymus protein. J Biol Chem, 248:3248-3254.

Elgin SC, Weintraub H. 1975. Chromosomal proteins and chromatin structure. Annu Rev Biochem, 44:725-774.

Faddy MJ. 2000. Follicle dynamics during ovarian ageing. Mol Cell Endocrinol, 163:43-48.

Fatemi M, Hermann A, Gowher H, Jeltsch A. 2002. Dnmt3a and Dnmt1 functionally cooperate during de novo methylation of DNA. Eur J Biochem, 269:4981-4984.

Georgel PT, Horowitz-Scherer RA, Adkins N, Woodcock CL, Wade PA, Hansen JC. 2003. Chromatin compaction by human MeCP2. Assembly of novel secondary chromatin structures in the absence of DNA methylation. J Biol Chem, 278:32181-32188.

Gu TP, Guo F, Yang H, Wu HP, Xu GF, Liu W, Xie ZG, Shi L, He X, Jin SG, Iqbal K, Shi YG, Deng Z, Szabo PE, Pfeifer GP, Li J, Xu GL. 2011. The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes. Nature, 477:606-610.

Hales BF, Grenier L, Lalancette C, Robaire B. 2011. Epigenetic programming: from gametes to blastocyst. Birth Defects Res A Clin Mol Teratol, 91:652-665.

Hamatani T, Falco G, Carter MG, Akutsu H, Stagg CA, Sharov AA, Dudekula DB, VanBuren V, Ko MS. 2004. Age-associated alteration of gene expression patterns in mouse oocytes. Hum Mol Genet, 13:2263-2278.

Hassold T, Hunt P. 2001. To err (meiotically) is human: the genesis of human aneuploidy. Nat Rev Genet, 2:280-291.

Hebbes TR, Thorne AW, Crane-Robinson C. 1988. A direct link between core histone acetylation and transcriptionally active chromatin. EMBO J, 7:1395-1402.

Hermann A, Goyal R, Jeltsch A. 2004. The Dnmt1 DNA-(cytosine-C5)-methyltransferase methylates DNA processively with high preference for hemimethylated target sites. J Biol Chem, 279:48350-48359.

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, 22:1607-1616.

Hiura H, Obata Y, Komiyama J, Shirai M, Kono T. 2006. Oocyte growth-dependent progression of maternal imprinting in mice. Genes Cells, 11:353-361.

Hornick JE, Duncan FE, Sun M, Kawamura R, Marko JF, Woodruff TK. 2015. Age-associated alterations in the micromechanical properties of chromosomes in the mammalian egg. J Assist Reprod Genet, 32:765-769.

Huffman SR, Pak Y, Rivera RM. 2015. Superovulation induces alterations in the epigenome of zygotes, and results in differences in gene expression at the blastocyst stage in mice, Mol Reprod Dev, 82:207-217.

Iqbal K, Jin SG, Pfeifer GP, Szabo PE. 2011. Reprogramming of the paternal genome upon fertilization involves genome-wide oxidation of 5-methylcytosine. Proc Natl Acad Sci U S A, 108:3642-3647.

Jones PL, Veenstra GJ, Wade PA, Vermaak D, Kass SU, Landsberger N, Strouboulis J, Wolffe AP. 1998. Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription. Nat Genet, 19:187-191.

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

Kageyama S, Liu H, Kaneko N, Ooga M, Nagata M, Aoki F. 2007. Alterations in epigenetic modifications during oocyte growth in mice. Reproduction, 133:85-94.

Kaludov NK, Wolffe AP. 2000. MeCP2 driven transcriptional repression in vitro: selectivity for methylated DNA, action at a distance and contacts with the basal transcription machinery. Nucleic Acids Res, 28:1921-1928.

Kantor B, Makedonski K, Shemer R, Razin A. 2003. Expression and localization of components of the histone deacetylases multiprotein repressory complexes in the mouse preimplantation embryo. Gene Expr Patterns, 3:697-702.

Keshet I, Lieman-Hurwitz J, Cedar H. 1986. DNA methylation affects the formation of active chromatin. Cell, 44:535-543.

Kim JM, Liu H, Tazaki M, Nagata M, Aoki F. 2003. Changes in histone acetylation during mouse oocyte meiosis. The Journal of cell biology, 162:37-46.

Kishi N, Macklis JD. 2004. MECP2 is progressively expressed in post-migratory neurons and is involved in neuronal maturation rather than cell fate decisions. Mol Cell Neurosci, 27:306-321.

Kondo Y, Shen L, Ahmed S, Boumber Y, Sekido Y, Haddad BR, Issa JP. 2008. Downregulation of histone H3 lysine 9 methyltransferase G9a induces centrosome disruption and chromosome instability in cancer cells. PloS one, 3:e2037.

Kota SK, Feil R. 2010. Epigenetic transitions in germ cell development and meiosis. Dev Cell, 19:675-686.

Kouzarides T. 2007. Chromatin modifications and their function. Cell, 128:693-705.

Lachner M, O'Carroll D, Rea S, Mechtler K, Jenuwein T. 2001. Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins. Nature, 410:116-120.

Lachner M, Sengupta R, Schotta G, Jenuwein T. 2004. Trilogies of histone lysine methylation as epigenetic landmarks of the eukaryotic genome. Cold Spring Harb Symp Quant Biol, 69:209-218.

Lande-Diner L, Zhang J, Ben-Porath I, Amariglio N, Keshet I, Hecht M, Azuara V, Fisher AG, Rechavi G, Cedar H. 2007. Role of DNA methylation in stable gene repression. J Biol Chem, 282:12194-12200.

Lepikhov K, Walter J. 2004. Differential dynamics of histone H3 methylation at positions K4 and K9 in the mouse zygote. BMC Dev Biol, 4:12.

Lepikhov K, Wossidlo M, Arand J, Walter J. 2010. DNA methylation reprogramming and DNA repair in the mouse zygote. Int J Dev Biol, 54:1565-1574.

Lopes FL, Fortier AL, Darricarrere N, Chan D, Arnold DR, Trasler JM. 2009. Reproductive and epigenetic outcomes associated with aging mouse oocytes. Hum Mol Genet, 18:2032-2044.

Lucifero D, Mann MR, Bartolomei MS, Trasler JM. 2004. Gene-specific timing and epigenetic memory in oocyte imprinting. Hum Mol Genet, 13:839-849.

Lucifero D, Mertineit C, Clarke HJ, Bestor TH, Trasler JM. 2002. Methylation dynamics of imprinted genes in mouse germ cells. Genomics, 79:530-538.

Manosalva I, Gonzalez A. 2009. Aging alters histone H4 acetylation and CDC2A in mouse germinal vesicle stage oocytes. Biol Reprod, 81:1164-1171.

Manosalva I, González A. 2010. Aging changes the chromatin configuration and histone methylation of mouse oocytes at germinal vesicle stage. Theriogenology, 74:1539-1547.

Marchi M, Guarda A, Bergo A, Landsberger N, Kilstrup-Nielsen C, Ratto GM, Costa M. 2007. Spatio-temporal dynamics and localization of MeCP2 and pathological mutants in living cells. Epigenetics, 2:187-197.

Market-Velker BA, Zhang L, Magri LS, Bonvissuto AC, Mann MR. 2010. Dual effects of superovulation: loss of maternal and paternal imprinted methylation in a dose-dependent manner. Hum Mol Genet, 19:36-51.

Masala L, Burrai GP, Bellu E, Ariu F, Bogliolo L, Ledda S, Bebbere D. 2017. Methylation dynamics during folliculogenesis and early embryo development in sheep. Reproduction, 153:605-619.

Mayer W, Niveleau A, Walter J, Fundele R, Haaf T. 2000. Demethylation of the zygotic paternal genome. Nature, 403:501-502.

Monk M, Boubelik M, 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.

Nakamura T, Liu YJ, Nakashima H, Umehara H, Inoue K, Matoba S, Tachibana M, Ogura A, Shinkai Y, Nakano T. 2012. PGC7 binds histone H3K9me2 to protect against conversion of 5mC to 5hmC in early embryos. Nature, 486:415-419.

Nan X, Ng HH, Johnson CA, Laherty CD, Turner BM, Eisenman RN, Bird A. 1998. Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex. Nature, 393:386-389.

Ohki I, Shimotake N, Fujita N, Jee J, Ikegami T, Nakao M, Shirakawa M. 2001. Solution structure of the methyl-CpG binding domain of human MBD1 in complex with methylated DNA. Cell, 105:487-497.

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

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, 10:475-478.

Pan H, Ma P, Zhu W, Schultz RM. 2008. Age-associated increase in aneuploidy and changes in gene expression in mouse eggs. Dev Biology, 316:397-407.

Pan H, O'Brien M J, Wigglesworth K, Eppig JJ, Schultz RM. 2005. Transcript profiling during mouse oocyte development and the effect of gonadotropin priming and development in vitro. Dev Biol, 286:493-506.

Peat JR, Dean W, Clark SJ, Krueger F, Smallwood SA, Ficz G, Kim JK, Marioni JC, Hore TA, Reik W. 2014. Genome-wide bisulfite sequencing in zygotes identifies demethylation targets and maps the contribution of TET3 oxidation. Cell Rep, 9:1990-2000.

Pennings S, Allan J, Davey CS. 2005. DNA methylation, nucleosome formation and positioning. Brief Funct Genomic Proteomic, 3:351-361.

Peters AH, Kubicek S, Mechtler K, O'Sullivan RJ, Derijck AA, Perez-Burgos L, Kohlmaier A, Opravil S, Tachibana M, Shinkai Y, Martens JH, Jenuwein T. 2003. Partitioning and plasticity of repressive histone methylation states in mammalian chromatin. Mol Cell, 12:1577-1589.

Peters AH, O'Carroll D, Scherthan H, Mechtler K, Sauer S, Schofer C, Weipoltshammer K, Pagani M, Lachner M, Kohlmaier A, Opravil S, Doyle M, Sibilia M, Jenuwein T. 2001. Loss of the Suv39h histone methyltransferases impairs mammalian heterochromatin and genome stability. Cell, 107:323-337.

Plachot M. 2001. Chromosomal abnormalities in oocytes. Molecular and Cellular Endocrinology, 183, Supplement 1:S59-S63.

Plasschaert RN, Bartolomei MS. 2014. Genomic imprinting in development, growth, behavior and stem cells. Development, 141:1805-1813.

Qiao J, Wang ZB, Feng HL, Miao YL, Wang Q, Yu Y, Wei YC, Yan J, Wang WH, Shen W, Sun SC, Schatten H, Sun QY. 2014. The root of reduced fertility in aged women and possible therapentic options: current status and future perspects. Mol Aspects Med, 38:54-85.

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, 245:304-314.

Rougier N, Bourc'his D, Gomes DM, Niveleau A, Plachot M, Paldi A, Viegas-Pequignot E. 1998. Chromosome methylation patterns during mammalian preimplantation development. Genes Dev, 12:2108-2113.

Ruddock-D'Cruz NT, Xue J, Wilson KJ, Heffernan C, Prashadkumar S, Cooney MA, Sanchez-Partida LG, French AJ, Holland MK. 2008. Dynamic changes in the localization of five members of the methyl binding domain (MBD) gene family during murine and bovine preimplantation embryo development. Mol Reprod Dev, 75:48-59.

Salmina K, Huna A, Inashkina I, Belyayev A, Krigerts J, Pastova L, Vazquez-Martin A, Erenpreisa J. 2017. Nucleolar aggresomes mediate release of pericentric heterochromatin and nuclear destruction of genotoxically treated cancer cells. Nucleus, 8:205-221.

Sanford JP, Clark HJ, Chapman VM, Rossant J. 1987. Differences in DNA methylation during oogenesis and spermatogenesis and their persistence during early embryogenesis in the mouse. Genes Dev, 1:1039-1046.

Santos F, Hendrich B, Reik W, Dean W. 2002. Dynamic reprogramming of DNA methylation in the early mouse embryo. Dev Biol, 241:172-182.

Santos F, Peters AH, Otte AP, Reik W, Dean W. 2005. Dynamic chromatin modifications characterise the first cell cycle in mouse embryos. Dev Biol, 280:225-236.

Sato A, Otsu E, Negishi H, Utsunomiya T, Arima T. 2007. Aberrant DNA methylation of imprinted loci in superovulated oocytes. Hum Reprod, 22:26-35.

Schultz DC, Ayyanathan K, Negorev D, Maul GG, Rauscher FJ, 3rd. 2002. SETDB1: a novel KAP-1-associated histone H3, lysine 9-specific methyltransferase that contributes to HP1-mediated silencing of euchromatic genes by KRAB zinc-finger proteins. Genes Dev, 16:919-932.

Sharif J, Muto M, Takebayashi S, Suetake I, Iwamatsu A, Endo TA, Shinga J, Mizutani-Koseki Y, Toyoda T, Okamura K, Tajima S, Mitsuya K, Okano M, Koseki H. 2007. The SRA protein Np95 mediates epigenetic inheritance by recruiting Dnmt1 to methylated DNA. Nature, 450:908-912.

Shi W, Haaf T. 2002. Aberrant methylation patterns at the two-cell stage as an indicator of early developmental failure. Mol Reprod Dev, 63:329-334.

Sinclair DA, Guarente L. 1997. Extrachromosomal rDNA circles--a cause of aging in yeast. Cell, 91:1033-1042.

Singleton MK, Gonzales ML, Leung KN, Yasui DH, Schroeder DI, Dunaway K, LaSalle JM. 2011. MeCP2 is required for global heterochromatic and nucleolar changes during activity-dependent neuronal maturation. Neurobiol Dis, 43:190-200.

Song C, Feodorova Y, Guy J, Peichl L, Jost KL, Kimura H, Cardoso MC, Bird A, Leonhardt H, Joffe B, Solovei I. 2014. DNA methylation reader MECP2: cell type- and differentiation stage-specific protein distribution. Epigenetics Chromatin, 7:17.

Tachibana M, Nozaki M, Takeda N, Shinkai Y. 2007. Functional dynamics of H3K9 methylation during meiotic prophase progression. EMBO J, 26:3346-3359.

Tachibana M, Sugimoto K, Nozaki M, Ueda J, Ohta T, Ohki M, Fukuda M, Takeda N, Niida H, Kato H, Shinkai Y. 2002. G9a histone methyltransferase plays a dominant role in euchromatic histone H3 lysine 9 methylation and is essential for early embryogenesis. Genes Dev, 16:1779-1791.

Talbert GB. 1971. Effect of maternal age on postimplantation reproductive failure in mice. J Reprod Fertil, 24:449-452.

Turner BM, 2008. Chromatin and Gene Regulation: Molecular Mechanisms in Epigenetics. Wiley.

van den Berg IM, Eleveld C, van der Hoeven M, Birnie E, Steegers EA, Galjaard RJ, Laven JS, van Doorninck JH. 2011. Defective deacetylation of histone 4 K12 in human oocytes is associated with advanced maternal age and chromosome misalignment. Hum Reprod, 26:1181-1190.

van Kooij RJ, Looman CW, Habbema JD, Dorland M, te Velde ER. 1996. Age-dependent decrease in embryo implantation rate after in vitro fertilization. Fertil Steril, 66:769-775.

Vanhooren V, Libert C. 2013. The mouse as a model organism in aging research: usefulness, pitfalls and possibilities. Ageing Res Rev, 12:8-21.

Ventura SJ, Curtin SC, Abma JC, Henshaw SK. 2012. Estimated pregnancy rates and rates of pregnancy outcomes for the United States, 1990-2008. Natl Vital Stat Rep, 60:1-21.

Wakefield RI, Smith BO, Nan X, Free A, Soteriou A, Uhrin D, Bird AP, Barlow PN. 1999. The solution structure of the domain from MeCP2 that binds to methylated DNA. J Mol Biol, 291:1055-1065.

Watt F, Molloy PL. 1988. Cytosine methylation prevents binding to DNA of a HeLa cell transcription factor required for optimal expression of the adenovirus major late promoter. Genes Dev, 2:1136-1143.

Weber M, Hellmann I, Stadler MB, Ramos L, Paabo S, Rebhan M, Schubeler D. 2007. Distribution, silencing potential and evolutionary impact of promoter DNA methylation in the human genome. Nat Genet, 39:457-466.

Wossidlo M, Nakamura T, Lepikhov K, Marques CJ, Zakhartchenko V, Boiani M, Arand J, Nakano T, Reik W, Walter J. 2011. 5-Hydroxymethylcytosine in the mammalian zygote is linked with epigenetic reprogramming. Nat Commun, 2:241.

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, 29:643-650.

Zentner GE, Henikoff S. 2013. Regulation of nucleosome dynamics by histone modifications. Nat Struct Mol Biol, 20:259-266.

Zou X, Ma W, Solov'yov IA, Chipot C, Schulten K. 2012. Recognition of methylated DNA through methyl-CpG binding domain proteins. Nucleic Acids Res, 40:2747-2758.

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