Register      Login
Reproduction, Fertility and Development Reproduction, Fertility and Development Society
Vertebrate reproductive science and technology
REVIEW

One-carbon metabolism and epigenetic regulation of embryo development

Juan Xu A and Kevin D. Sinclair A B
+ Author Affiliations
- Author Affiliations

A School of Bioscience, University of Nottingham, Sutton Bonington, Leicestershire LE12 5RD, UK.

B Corresponding author. Email: kevin.sinclair@nottingham.ac.uk

Reproduction, Fertility and Development 27(4) 667-676 https://doi.org/10.1071/RD14377
Submitted: 6 October 2014  Accepted: 8 January 2015   Published: 25 February 2015

Abstract

One-carbon (1C) metabolism consists of an integrated series of metabolic pathways that include the folate cycle and methionine remethylation and trans-sulfuration pathways. Most, but not all, 1C metabolic enzymes are expressed in somatic cells of the ovary, mammalian oocytes and in preimplantation embryos. The metabolic implications of this, with regard to the provision of methyl donors (e.g. betaine) and 1C cofactors (e.g. vitamin B12), together with consequences of polymorphic variances in genes encoding 1C enzymes, are not fully understood but are the subject of ongoing investigations at the authors’ laboratory. However, deficiencies in 1C-related substrates and/or cofactors during the periconception period are known to lead to epigenetic alterations in DNA and histone methylation in genes that regulate key developmental processes in the embryo. Such epigenetic modifications have been demonstrated to negatively impact on the subsequent health and metabolism of offspring. For this reason, parental nutrition around the time of conception has become a focal point of investigation in many laboratories with the aim of providing improved nutritional advice to couples. These issues are considered in detail in this article, which offers a contemporary overview of the effects of 1C metabolism on epigenetic programming in mammalian gametes and the early embryo.

Additional keywords: epigenetics, folate, methionine, oocyte, preimplantation development, spermatogenesis.


References

Abdalla, H., Yoshizawa, Y., and Hochi, S. (2009). Active demethylation of paternal genome in mammalian zygotes. J. Reprod. Dev. 55, 356–360.
Active demethylation of paternal genome in mammalian zygotes.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXhsFOmtLnK&md5=622fc346ac7be2c8c0465a174f8af04dCAS | 19721335PubMed |

Afman, L. A., Van Der Put, N. M., Thomas, C. M., Trijbels, J. M., and Blom, H. J. (2001). Reduced vitamin B12 binding by transcobalamin II increases the risk of neural tube defects. QJM-Int J. Med. 94, 159–166.
Reduced vitamin B12 binding by transcobalamin II increases the risk of neural tube defects.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD3M7mt1WjsQ%3D%3D&md5=f841d7db8328b20c63c3f658a2a7137cCAS |

Akiyama, T., Kim, J. M., Nagata, M., and Aoki, F. (2004). Regulation of histone acetylation during meiotic maturation in mouse oocytes. Mol. Reprod. Dev. 69, 222–227.
Regulation of histone acetylation during meiotic maturation in mouse oocytes.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXnsVKns7k%3D&md5=e1fbbcf9e96e14fd1957aec106f722cdCAS | 15293224PubMed |

Allegra, C. J., Chabner, B. A., Drake, J. C., Lutz, R., Rodbard, D., and Jolivet, J. (1985). Enhanced inhibition of thymidylate synthase by methotrexate polyglutamates. J. Biol. Chem. 260, 9720–9726.
| 1:CAS:528:DyaL2MXltlCltL8%3D&md5=6176ec7fb3b77b3a12bb83f5d863535aCAS | 2410416PubMed |

Allegra, C. J., Hoang, K., Yeh, G. C., Drake, J. C., and Baram, J. (1987). Evidence for direct inhibition of de novo purine synthesis in human MCF-7 breast cells as a principal mode of metabolic inhibition by methotrexate. J. Biol. Chem. 262, 13 520–13 526.
| 1:CAS:528:DyaL2sXlvFSmsL4%3D&md5=6d734be9d59a2fc95f91c734411c8da2CAS |

Altobelli, G., Bogdarina, I. G., Stupka, E., Clark, A. J., and Langley-Evans, S. (2013). Genome-wide methylation and gene expression changes in newborn rats following maternal protein restriction and reversal by folic acid. PLoS One 8, e82989.
Genome-wide methylation and gene expression changes in newborn rats following maternal protein restriction and reversal by folic acid.Crossref | GoogleScholarGoogle Scholar | 24391732PubMed |

Bailey, L. B., and Gregory, J. F. (1999). Polymorphisms of methylenetetrahydrofolate reductase and other enzymes: metabolic significance, risks and impact on folate requirement. J. Nutr. 129, 919–922.
| 1:CAS:528:DyaK1MXivVyguro%3D&md5=b2ba0de186256b6115b9b32e193e5b4dCAS | 10222379PubMed |

Baylin, S. B., Belinsky, S. A., and Herman, J. G. (2000). Aberrant methylation of gene promoters in cancer: concepts, misconcepts, and promise. J. Natl Cancer Inst. 92, 1460–1461.
Aberrant methylation of gene promoters in cancer: concepts, misconcepts, and promise.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD3M%2Fmt1SltA%3D%3D&md5=6ffd59dfb81ae850efd921c70bf2b179CAS | 10995795PubMed |

Beaujean, N., Taylor, J. E., McGarry, M., Gardner, J. O., Wilmut, I., Loi, P., Ptak, G., Galli, C., Lazzari, G., Bird, A., Young, L. E., and Meehan, R. R. (2004). The effect of interspecific oocytes on demethylation of sperm DNA. Proc. Natl Acad. Sci. USA 101, 7636–7640.
The effect of interspecific oocytes on demethylation of sperm DNA.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXktlOltb0%3D&md5=e5e6b93d8977d1209cc2793c8aaea9e4CAS | 15136736PubMed |

Benchaib, M., Braun, V., Ressnikof, D., Lornage, J., Durand, P., Niveleau, A., and Guerin, J. F. (2005). Influence of global sperm DNA methylation on IVF results. Hum. Reprod. 20, 768–773.
Influence of global sperm DNA methylation on IVF results.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXhsFSgtrk%3D&md5=dfde9d5a46a3af215e7ce5ed9e0d3419CAS | 15640258PubMed |

Bjerling, P., Silverstein, R. A., Thon, G., Caudy, A., Grewal, S., and Ekwall, K. (2002). Functional divergence between histone deacetylases in fission yeast by distinct cellular localization and in vivo specificity. Mol. Cell. Biol. 22, 2170–2181.
Functional divergence between histone deacetylases in fission yeast by distinct cellular localization and in vivo specificity.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38Xit1Kitro%3D&md5=72b252a553da4ce3cdba6515f8473d11CAS | 11884604PubMed |

Braun, R. E. (2001). Packaging paternal chromosomes with protamine. Nat. Genet. 28, 10–12.
Packaging paternal chromosomes with protamine.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXjt1Wquro%3D&md5=094cac694649aa4eb74502fc63c72222CAS | 11326265PubMed |

Brewer, L., Corzett, M., and Balhorn, R. (2002). Condensation of DNA by spermatid basic nuclear proteins. J. Biol. Chem. 277, 38 895–38 900.
Condensation of DNA by spermatid basic nuclear proteins.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38Xns1Cnur0%3D&md5=b6b81c12bb5f408cc07fa5c3d77bbfdbCAS |

Cantone, I., and Fisher, A. G. (2013). Epigenetic programming and reprogramming during development. Nat. Struct. Mol. Biol. 20, 282–289.
Epigenetic programming and reprogramming during development.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXjsFOnsbk%3D&md5=f3e6ee6e41e4f405e8e58e0cf1f96cc2CAS | 23463313PubMed |

Carone, B. R., Fauquier, L., Habib, N., Shea, J. M., Hart, C. E., Li, R., Bock, C., Li, C., Gu, H., Zamore, P. D., Meissner, A., Weng, Z., Hofmann, H. A., Friedman, N., and Rando, O. J. (2010). Paternally induced transgenerational environmental reprogramming of metabolic gene expression in mammals. Cell 143, 1084–1096.
Paternally induced transgenerational environmental reprogramming of metabolic gene expression in mammals.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhs1agtrbE&md5=c8e9f278a6df95c4af7fff6205e5b887CAS | 21183072PubMed |

Caudill, M. A., Wang, J. C., Melnyk, S., Pogribny, I. P., Jernigan, S., Collins, M. D., Santos-Guzman, J., Swendseid, M. E., Cogger, E. A., and James, S. J. (2001). Intracellular S-adenosylhomocysteine concentrations predict global DNA hypomethylation in tissues of methyl-deficient cystathionine beta-synthase heterozygous mice. J. Nutr. 131, 2811–2818.
| 1:CAS:528:DC%2BD3MXosVyksLc%3D&md5=fde6773538811dc75c6758c737e8a469CAS | 11694601PubMed |

Cedar, H., and Bergman, Y. (2009). Linking DNA methylation and histone modification: patterns and paradigms. Nat. Rev. Genet. 10, 295–304.
Linking DNA methylation and histone modification: patterns and paradigms.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXksF2rsL0%3D&md5=956a09561498177071ed649c819cb73bCAS | 19308066PubMed |

Cichowicz, D. J., and Shane, B. (1987). Mammalian folylpoly-gamma-glutamate synthetase. 2. Substrate specificity and kinetic properties. Biochemistry 26, 513–521.
Mammalian folylpoly-gamma-glutamate synthetase. 2. Substrate specificity and kinetic properties.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL2sXks1ersA%3D%3D&md5=81c17d55fa13c57abc636502895048ddCAS | 3828321PubMed |

Cooney, C. A., Dave, A. A., and Wolff, G. L. (2002). Maternal methyl supplements in mice affect epigenetic variation and DNA methylation of offspring. J. Nutr. 132, 2393S–2400S.
| 1:CAS:528:DC%2BD38XmtF2qsro%3D&md5=d620575b337a43bc6b6f92a9271de14dCAS | 12163699PubMed |

Coppedè, F., Lorenzoni, V., and Migliore, L. (2013). The reduced folate carrier (RFC-1) 80A>G polymorphism and maternal risk of having a child with Down syndrome: a meta-analysis. Nutrients 5, 2551–2563.
The reduced folate carrier (RFC-1) 80A>G polymorphism and maternal risk of having a child with Down syndrome: a meta-analysis.Crossref | GoogleScholarGoogle Scholar | 23857226PubMed |

De La Fuente, R. (2006). Chromatin modifications in the germinal vesicle (GV) of mammalian oocytes. Dev. Biol. 292, 1–12.
Chromatin modifications in the germinal vesicle (GV) of mammalian oocytes.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XjtFGmtL4%3D&md5=90f4043a69d445b51543a212f63f4652CAS | 16466710PubMed |

De La Fuente, R., Viveiros, M. M., Burns, K. H., Adashi, E. Y., Matzuk, M. M., and Eppig, J. J. (2004). Major chromatin remodeling in the germinal vesicle (GV) of mammalian oocytes is dispensable for global transcriptional silencing but required for centromeric heterochromatin function. Dev. Biol. 275, 447–458.
Major chromatin remodeling in the germinal vesicle (GV) of mammalian oocytes is dispensable for global transcriptional silencing but required for centromeric heterochromatin function.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXovVKltbc%3D&md5=39abdba5e1b592c4d24844324a2e5d5fCAS | 15501230PubMed |

De Marco, P., Calevo, M. G., Moroni, A., Merello, E., Raso, A., Finnell, R. H., Zhu, H., Andreussi, L., Cama, A., and Capra, V. (2003). Reduced folate carrier polymorphism (80A→G) and neural tube defects. Eur. J. Hum. Genet. 11, 245–252.
Reduced folate carrier polymorphism (80A→G) and neural tube defects.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXisFKgtrc%3D&md5=b521fe0b968dd94fcc1ec773da786c7dCAS | 12673279PubMed |

de Ruijter, A. J., van Gennip, A. H., Caron, H. N., Kemp, S., and van Kuilenburg, A. B. (2003). Histone deacetylases (HDACs): characterization of the classical HDAC family. Biochem. J. 370, 737–749.
Histone deacetylases (HDACs): characterization of the classical HDAC family.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXhvFKiu7o%3D&md5=f24836003452a9b71817c82f427ca9a7CAS | 12429021PubMed |

Dominguez-Salas, P., Moore, S. E., Baker, M. S., Bergen, A. W., Cox, S. E., Dyer, R. A., Fulford, A. J., Guan, Y., Laritsky, E., Silver, M. J., Swan, G. E., Zeisel, S. H., Innis, S. M., Waterland, R. A., Prentice, A. M., and Hennig, B. J. (2014). Maternal nutrition at conception modulates DNA methylation of human metastable epialleles. Nat. Commun. 5, 3746.
Maternal nutrition at conception modulates DNA methylation of human metastable epialleles.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXitVShsb7E&md5=74459f9cba32439371f92efd44fa4a56CAS | 24781383PubMed |

Dufficy, L., Naumovski, N., Ng, X., Blades, B., Yates, Z., Travers, C., Lewis, P., Sturm, J., Veysey, M., Roach, P. D., and Lucock, M. D. (2006). G80A reduced folate carrier SNP influences the absorption and cellular translocation of dietary folate and its association with blood pressure in an elderly population. Life Sci. 79, 957–966.
G80A reduced folate carrier SNP influences the absorption and cellular translocation of dietary folate and its association with blood pressure in an elderly population.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XntFSnsb0%3D&md5=c73068a62974b2938a607ce7e3113bb8CAS | 16750224PubMed |

Eden, S., and Cedar, H. (1994). Role of DNA methylation in the regulation of transcription. Curr. Opin. Genet. Dev. 4, 255–259.
Role of DNA methylation in the regulation of transcription.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2cXmsVOhsrg%3D&md5=724ab0d0d8df4f098a2737606326e183CAS | 8032203PubMed |

Edwards, C. A., and Ferguson-Smith, A. C. (2007). Mechanisms regulating imprinted genes in clusters. Curr. Opin. Cell Biol. 19, 281–289.
Mechanisms regulating imprinted genes in clusters.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXmsFKmsrc%3D&md5=d42de7416a84f98b38f7e97d01643245CAS | 17467259PubMed |

Erhardt, S., Su, I. H., Schneider, R., Barton, S., Bannister, A. J., Perez-Burgos, L., Jenuwein, T., Kouzarides, T., Tarakhovsky, A., and Surani, M. A. (2003). Consequences of the depletion of zygotic and embryonic enhancer of zeste 2 during preimplantation mouse development. Development 130, 4235–4248.
Consequences of the depletion of zygotic and embryonic enhancer of zeste 2 during preimplantation mouse development.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXnvVWnt78%3D&md5=d691ef103875dd4fb2ef908825a4c11dCAS | 12900441PubMed |

Feil, R., and Fraga, M. F. (2011). Epigenetics and the environment: emerging patterns and implications. Nat. Rev. Genet. 13, 97–109.

Forneris, F., Binda, C., Adamo, A., Battaglioli, E., and Mattevi, A. (2007). Structural basis of LSD1-CoREST selectivity in histone H3 recognition. J. Biol. Chem. 282, 20 070–20 074.
Structural basis of LSD1-CoREST selectivity in histone H3 recognition.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXnsFWntr0%3D&md5=d727382b059855ee7ebc186c0feb4a65CAS |

Gellekink, H., Blom, H. J., and den Heijer, M. (2007). Associations of common polymorphisms in the thymidylate synthase, reduced folate carrier and 5-aminoimidazole-4-carboxamide ribonucleotide transformylase/inosine monophosphate cyclohydrolase genes with folate and homocysteine levels and venous thrombosis risk. Clin. Chem. Lab. Med. 45, 471–476.
Associations of common polymorphisms in the thymidylate synthase, reduced folate carrier and 5-aminoimidazole-4-carboxamide ribonucleotide transformylase/inosine monophosphate cyclohydrolase genes with folate and homocysteine levels and venous thrombosis risk.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXlsVWnt7Y%3D&md5=8ee259e2ac1a7f38bb7ad370df58f799CAS | 17439323PubMed |

Gómez-Gómez, Y., Organista-Nava, J., Rangel-Rodriguez, C. A., Illades-Aguiar, B., Moreno-Godínez, M. E., Alarcón-Romero, L. D., and Leyva-Vázquez, M. A. (2014). Effect of folylpolyglutamate synthase A22G polymorphism on the risk and survival of patients with acute lymphoblastic leukemia. Oncol. Lett. 8, 731–735.
| 25013492PubMed |

Gong, L., Pan, Y. X., and Chen, H. (2010). Gestational low protein diet in the rat mediates Igf2 gene expression in male offspring via altered hepatic DNA methylation. Epigenetics 5, 619–626.
Gestational low protein diet in the rat mediates Igf2 gene expression in male offspring via altered hepatic DNA methylation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhsFyrtbbF&md5=7c0e94b284222dbab705e517f5bd2cbfCAS | 20671425PubMed |

Grenier, L., Robaire, B., and Hales, B. F. (2010). Paternal exposure to cyclophosphamide affects the progression of sperm chromatin decondensation and activates a DNA damage response in the prepronuclear rat zygote. Biol. Reprod. 83, 195–204.
Paternal exposure to cyclophosphamide affects the progression of sperm chromatin decondensation and activates a DNA damage response in the prepronuclear rat zygote.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXpslSntLo%3D&md5=2390051bc379fbb37587a05cd77b5876CAS | 20393171PubMed |

Gu, H., Zhu, P., Yan, L., Li, R., Hu, B., Lian, Y., Yan, J., Ren, X., Lin, S., Li, J., et al. (2014). The DNA methylation landscape of human early embryos. Nature 511, 606–610.
The DNA methylation landscape of human early embryos.Crossref | GoogleScholarGoogle Scholar |

Hales, B. F., Grenier, L., Lalancette, C., and Robaire, B. (2011). Epigenetic programming: from gametes to blastocyst. Birth Defects Res. 91, 652–665.
Epigenetic programming: from gametes to blastocyst.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXpvVyhurs%3D&md5=2eaa21ba5bf626f9ef1d382b806e76a2CAS |

Hammoud, S. S., Nix, D. A., Zhang, H., Purwar, J., Carrell, D. T., and Cairns, B. R. (2009). Distinctive chromatin in human sperm packages genes for embryo development. Nature 460, 473–478.
| 1:CAS:528:DC%2BD1MXnt1Sht7w%3D&md5=c2ccc7d918fa5f510adb39b7504a311bCAS | 19525931PubMed |

Hammoud, S. S., Nix, D. A., Hammoud, A. O., Gibson, M., Cairns, B. R., and Carrell, D. T. (2011). Genome-wide analysis identifies changes in histone retention and epigenetic modifications at developmental and imprinted gene loci in the sperm of infertile men. Hum. Reprod. 26, 2558–2569.
Genome-wide analysis identifies changes in histone retention and epigenetic modifications at developmental and imprinted gene loci in the sperm of infertile men.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhtVynsrzI&md5=09b6d1eb367a642125bab2966ba6dc1dCAS | 21685136PubMed |

Hemberger, M., Dean, W., and Reik, W. (2009). Epigenetic dynamics of stem cells and cell lineage commitment: digging Waddington’s canal. Nat. Rev. Mol. Cell Biol. 10, 526–537.
Epigenetic dynamics of stem cells and cell lineage commitment: digging Waddington’s canal.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXosFWhtrY%3D&md5=7bfcf8e7106e6443222982f4e06a95a3CAS | 19603040PubMed |

Hochberg, Z., Feil, R., Constancia, M., Fraga, M., Junien, C., Carel, J. C., Boileau, P., Le Bouc, Y., Deal, C. L., Lillycrop, K., Scharfmann, R., Sheppard, A., Skinner, M., Szyf, M., Waterland, R. A., Waxman, D. J., Whitelaw, E., Ong, K., and Albertsson-Wikland, K. (2011). Child health, developmental plasticity, and epigenetic programming. Endocr. Rev. 32, 159–224.
Child health, developmental plasticity, and epigenetic programming.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXmsFWmsbo%3D&md5=568c0ae3e6c585ed2dad6e421e3422d9CAS | 20971919PubMed |

Houshdaran, S., Cortessis, V. K., Siegmund, K., Yang, A., Laird, P. W., and Sokol, R. Z. (2007). Widespread epigenetic abnormalities suggest a broad DNA methylation erasure defect in abnormal human sperm. PLoS ONE 2, e1289.
Widespread epigenetic abnormalities suggest a broad DNA methylation erasure defect in abnormal human sperm.Crossref | GoogleScholarGoogle Scholar | 18074014PubMed |

Hud, N. V., and Vilfan, I. D. (2005). Toroidal DNA condensates: unraveling the fine structure and the role of nucleation in determining size. Annu. Rev. Biophys. Biomol. Struct. 34, 295–318.
Toroidal DNA condensates: unraveling the fine structure and the role of nucleation in determining size.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXlslCku7g%3D&md5=8fb118241790b5327af29812512bd742CAS | 15869392PubMed |

Ikeda, S., Namekawa, T., Sugimoto, M., and Kume, S. (2010). Expression of methylation pathway enzymes in bovine oocytes and preimplantation embryos. J. Exp. Zool. A Ecol. Genet. Physiol. 313, 129–136.
| 20073048PubMed |

Illingworth, R. S., and Bird, A. P. (2009). CpG islands: ‘a rough guide’. FEBS Lett. 583, 1713–1720.
CpG islands: ‘a rough guide’.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXmsVCmsrc%3D&md5=18939b7eebae5b1447bec78a7697676fCAS | 19376112PubMed |

Jhee, K. H., and Kruger, W. D. (2005). The role of cystathionine beta-synthase in homocysteine metabolism. Antioxid. Redox Signal. 7, 813–822.
The role of cystathionine beta-synthase in homocysteine metabolism.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXktVWit7Y%3D&md5=50c7d6f6b03ef0516ea1aff46eb94531CAS | 15890029PubMed |

Jones, P. A. (2012). Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat. Rev. Genet. 13, 484–492.
Functions of DNA methylation: islands, start sites, gene bodies and beyond.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38Xns1SqtLw%3D&md5=18970a5146b1c2e9beaf22c856fedd21CAS | 22641018PubMed |

Kaelin, W. G., and McKnight, S. L. (2013). Influence of metabolism on epigenetics and disease. Cell 153, 56–69.
Influence of metabolism on epigenetics and disease.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXltVemtrk%3D&md5=668c5fbc975c0ced3133eaceb7fee3f0CAS | 23540690PubMed |

Kageyama, S., Liu, H., Kaneko, N., Ooga, M., Nagata, M., and Aoki, F. (2007). Alterations in epigenetic modifications during oocyte growth in mice. Reproduction 133, 85–94.
Alterations in epigenetic modifications during oocyte growth in mice.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXjs1aju78%3D&md5=145c5d1a498ae1da928bbd280fa2ad77CAS | 17244735PubMed |

Kim, J. M., Liu, H., Tazaki, M., Nagata, M., and Aoki, F. (2003). Changes in histone acetylation during mouse oocyte meiosis. J. Cell Biol. 162, 37–46.
Changes in histone acetylation during mouse oocyte meiosis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXltleksL4%3D&md5=bf8d0aab0957ea520f742e0e9c4b70dbCAS | 12835313PubMed |

Kwong, W. Y., Adamiak, S. J., Gwynn, A., Singh, R., and Sinclair, K. D. (2010). Endogenous folates and single-carbon metabolism in the ovarian follicle, oocyte and pre-implantation embryo. Reproduction 139, 705–715.
Endogenous folates and single-carbon metabolism in the ovarian follicle, oocyte and pre-implantation embryo.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXltFajtrs%3D&md5=61513d590257022fb3bffbc1de97fe94CAS | 20083604PubMed |

Lambrot, R., Xu, C., Saint-Phar, S., Chountalos, G., Cohen, T., Paquet, M., Suderman, M., Hallett, M., and Kimmins, S. (2013). Low paternal dietary folate alters the mouse sperm epigenome and is associated with negative pregnancy outcomes. Nat. Commun. 4, 2889.
Low paternal dietary folate alters the mouse sperm epigenome and is associated with negative pregnancy outcomes.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BC2c3lsVymsg%3D%3D&md5=ac308c4535915572406c2110481d5f5aCAS | 24326934PubMed |

Lee, M. B., Kooistra, M., Zhang, B., Slow, S., Fortier, A. L., Garrow, T. A., Lever, M., Trasler, J. M., and Baltz, J. M. (2012). Betaine homocysteine methyltransferase is active in the mouse blastocyst and promotes inner cell mass development. J. Biol. Chem. 287, 33094–33103.
Betaine homocysteine methyltransferase is active in the mouse blastocyst and promotes inner cell mass development.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38Xhtlyqs77P&md5=d84a7ddcb829ca1c8ba5dfa0a5810e7bCAS | 22847001PubMed |

Li, E. (2002). Chromatin modification and epigenetic reprogramming in mammalian development. Nat. Rev. Genet. 3, 662–673.
Chromatin modification and epigenetic reprogramming in mammalian development.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38Xmslagt7w%3D&md5=5b08812d334e242d683b623eb72ef246CAS | 12209141PubMed |

Li, Y., and O’Neill, C. (2012). Persistence of cytosine methylation of DNA following fertilisation in the mouse. PLoS ONE 7, e30687.
Persistence of cytosine methylation of DNA following fertilisation in the mouse.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38Xitlaqsb8%3D&md5=aa89b5a30091042ddf0d3faf3b7959bdCAS | 22292019PubMed |

Liu, H., Kim, J. M., and Aoki, F. (2004). Regulation of histone H3 lysine 9 methylation in oocytes and early pre-implantation embryos. Development 131, 2269–2280.
Regulation of histone H3 lysine 9 methylation in oocytes and early pre-implantation embryos.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXltlGrtrs%3D&md5=d89968e383a3de6977f6aa11fe440f18CAS | 15102709PubMed |

Luka, Z., Moss, F., Loukachevitch, L. V., Bornhop, D. J., and Wagner, C. (2011). Histone demethylase LSD1 is a folate-binding protein. Biochemistry 50, 4750–4756.
Histone demethylase LSD1 is a folate-binding protein.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXlslCju7g%3D&md5=8e9b6ac7a1d035689b446bba1f889f54CAS | 21510664PubMed |

Luka, Z., Pakhomova, S., Loukachevitch, L. V., Calcutt, M. W., Newcomer, M. E., and Wagner, C. (2014a). Crystal structure of the histone lysine specific demethylase LSD1 complexed with tetrahydrofolate. Protein Sci. 23, 993–998.
Crystal structure of the histone lysine specific demethylase LSD1 complexed with tetrahydrofolate.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXhtVShsL%2FE&md5=0a0debc5872061f0d688b2e667a31a51CAS | 24715612PubMed |

Luka, Z., Pakhomova, S., Loukachevitch, L. V., Newcomer, M. E., and Wagner, C. (2014b). Folate in demethylation: the crystal structure of the rat dimethylglycine dehydrogenase complexed with tetrahydrofolate. Biochem. Biophys. Res. Commun. 449, 392–398.
Folate in demethylation: the crystal structure of the rat dimethylglycine dehydrogenase complexed with tetrahydrofolate.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXpslajsbY%3D&md5=a33df2065077e11f32b59d9459aff65dCAS | 24858690PubMed |

Maloney, C. A., Hay, S. M., Young, L. E., Sinclair, K. D., and Rees, W. D. (2011). A methyl-deficient diet fed to rat dams during the peri-conception period programs glucose homeostasis in adult male but not female offspring. J. Nutr. 141, 95–100.
A methyl-deficient diet fed to rat dams during the peri-conception period programs glucose homeostasis in adult male but not female offspring.Crossref | GoogleScholarGoogle Scholar | 21106931PubMed |

Mattick, J. S., Amaral, P. P., Dinger, M. E., Mercer, T. R., and Mehler, M. F. (2009). RNA regulation of epigenetic processes. Bioessays 31, 51–59.
RNA regulation of epigenetic processes.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXjtFKnu7c%3D&md5=63539867a4baa4d240cf1f8926222143CAS | 19154003PubMed |

McGuire, J. J., Russell, C. A., and Balinska, M. (2000). Human cytosolic and mitochondrial folylpolyglutamate synthetase are electrophoretically distinct. Expression in antifolate-sensitive and -resistant human cell lines. J. Biol. Chem. 275, 13 012–13 016.
Human cytosolic and mitochondrial folylpolyglutamate synthetase are electrophoretically distinct. Expression in antifolate-sensitive and -resistant human cell lines.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXjtVaqsrc%3D&md5=220b53ce2d5cc68bb583b90e393b710aCAS |

Messerschmidt, D. M., Knowles, B. B., and Solter, D. (2014). DNA methylation dynamics during epigenetic reprogramming in the germline and preimplantation embryos. Genes Dev. 28, 812–828.
DNA methylation dynamics during epigenetic reprogramming in the germline and preimplantation embryos.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXnsVamuro%3D&md5=4aa4dd48a87a842df4bdf81f27baae70CAS | 24736841PubMed |

Miller, K. M., Tjeertes, J. V., Coates, J., Legube, G., Polo, S. E., Britton, S., and Jackson, S. P. (2010). Human HDAC1 and HDAC2 function in the DNA-damage response to promote DNA nonhomologous end-joining. Nat. Struct. Mol. Biol. 17, 1144–1151.
Human HDAC1 and HDAC2 function in the DNA-damage response to promote DNA nonhomologous end-joining.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhtVyiu73E&md5=0d7b60fe6a8183c9eaefeb35fc4f9f26CAS | 20802485PubMed |

Miranda, T. B., and Jones, P. A. (2007). DNA methylation: the nuts and bolts of repression. J. Cell. Physiol. 213, 384–390.
DNA methylation: the nuts and bolts of repression.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXhtFKnu7rF&md5=06a50508020bf956b12e5f2ce0fd10b1CAS | 17708532PubMed |

Mudrak, O., Chandra, R., Jones, E., Godfrey, E., and Zalensky, A. (2009). Reorganisation of human sperm nuclear architecture during formation of pronuclei in a model system. Reprod. Fertil. Dev. 21, 665–671.
| 1:CAS:528:DC%2BD1MXmsVCrur0%3D&md5=7f2a7ffb85ebcda3bf56e72ce23b4ef0CAS | 19486603PubMed |

Narayanan, S., McConnell, J., Little, J., Sharp, L., Piyathilake, C. J., Powers, H., Basten, G., and Duthie, S. J. (2004). Associations between two common variants C677T and A1298C in the methylenetetrahydrofolate reductase gene and measures of folate metabolism and DNA stability (strand breaks, misincorporated uracil, and DNA methylation status) in human lymphocytes in vivo. Cancer Epidemiol. Biomark. Prev. 13, 1436–1443.
| 1:CAS:528:DC%2BD2cXntFCks7Y%3D&md5=76d76da1a7c997c324aa125b5cdf96c6CAS |

Ng, S. F., Lin, R. C., Laybutt, D. R., Barres, R., Owens, J. A., and Morris, M. J. (2010). Chronic high-fat diet in fathers programs beta-cell dysfunction in female rat offspring. Nature 467, 963–966.
Chronic high-fat diet in fathers programs beta-cell dysfunction in female rat offspring.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhtlWlsr%2FF&md5=ca415b4e39fc64cf32472d30bf9682baCAS | 20962845PubMed |

Ooi, S. K., O’Donnell, A. H., and Bestor, T. H. (2009). Mammalian cytosine methylation at a glance. J. Cell Sci. 122, 2787–2791.
Mammalian cytosine methylation at a glance.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXhtFOgsb7L&md5=5154b1b097cc558afe344b703144de73CAS | 19657014PubMed |

Pietrzik, K., Bailey, L., and Shane, B. (2010). Folic acid and L-5-methyltetrahydrofolate: comparison of clinical pharmacokinetics and pharmacodynamics. Clin. Pharmacokinet. 49, 535–548.
Folic acid and L-5-methyltetrahydrofolate: comparison of clinical pharmacokinetics and pharmacodynamics.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhtFWgtbvK&md5=41052ed66b55c9c77f522261200eafedCAS | 20608755PubMed |

Reik, W., Dean, W., and Walter, J. (2001). Epigenetic reprogramming in mammalian development. Science 293, 1089–1093.
Epigenetic reprogramming in mammalian development.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXmtVWltL8%3D&md5=a4d32ea9cf4c51f15d70243c38da206cCAS | 11498579PubMed |

Rivera, R. M. (2010). Epigenetic aspects of fertilization and preimplantation development in mammals: lessons from the mouse. Systems Biology in Reproductive Medicine 56, 388–404.
Epigenetic aspects of fertilization and preimplantation development in mammals: lessons from the mouse.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhtFOitLjF&md5=883884dc0ea2c79a791208539c626ddaCAS | 20849224PubMed |

Senner, C. E. (2011). The role of DNA methylation in mammalian development. Reprod. Biomed. Online 22, 529–535.
The role of DNA methylation in mammalian development.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXpsVGgtL0%3D&md5=0c2686f5b57a9146016a27712bf29fbeCAS | 21498123PubMed |

Shelnutt, K. P., Kauwell, G. P., Gregory, J. F., Maneval, D. R., Quinlivan, E. P., Theriaque, D. W., Henderson, G. N., and Bailey, L. B. (2004). Methylenetetrahydrofolate reductase 677C→T polymorphism affects DNA methylation in response to controlled folate intake in young women. J. Nutr. Biochem. 15, 554–560.
Methylenetetrahydrofolate reductase 677C→T polymorphism affects DNA methylation in response to controlled folate intake in young women.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXntlenur8%3D&md5=8d22b628618aa9cd9b7c6af227013a4eCAS | 15350988PubMed |

Shen, L., Wu, H., Diep, D., Yamaguchi, S., D’Alessio, A. C., Fung, H. L., Zhang, K., and Zhang, Y. (2013). Genome-wide analysis reveals TET- and TDG-dependent 5-methylcytosine oxidation dynamics. Cell 153, 692–706.
Genome-wide analysis reveals TET- and TDG-dependent 5-methylcytosine oxidation dynamics.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXmt1CktLs%3D&md5=b2f5a762e7a343fc68d0ee96790ddef1CAS | 23602152PubMed |

Sinclair, K. D., and Watkins, A. J. (2014). Parental diet, pregnancy outcomes and offspring health: metabolic determinants in developing oocytes and embryos. Reprod. Fertil. Dev. 26, 99–114.
Parental diet, pregnancy outcomes and offspring health: metabolic determinants in developing oocytes and embryos.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXhvV2lsrnN&md5=3ac3f29bdad6ec6acbf9be025c38a092CAS |

Sinclair, K. D., Allegrucci, C., Singh, R., Gardner, D. S., Sebastian, S., Bispham, J., Thurston, A., Huntley, J. F., Rees, W. D., Maloney, C. A., Lea, R. G., Craigon, J., McEvoy, T. G., and Young, L. E. (2007). DNA methylation, insulin resistance, and blood pressure in offspring determined by maternal periconceptional B vitamin and methionine status. Proc. Natl Acad. Sci. USA 104, 19 351–19 356.
DNA methylation, insulin resistance, and blood pressure in offspring determined by maternal periconceptional B vitamin and methionine status.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXisVOjug%3D%3D&md5=27198a2594d37842d69953e3eb7c8b9aCAS |

Sirotnak, F. M., and Tolner, B. (1999). Carrier-mediated membrane transport of folates in mammalian cells. Annu. Rev. Nutr. 19, 91–122.
Carrier-mediated membrane transport of folates in mammalian cells.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1MXlt1ejs7k%3D&md5=d1231a2c5243f71eda08ac61b1dd569bCAS | 10448518PubMed |

Skinner, M. K. (2011). Environmental epigenetic transgenerational inheritance and somatic epigenetic mitotic stability. Epigenetics 6, 838–842.
Environmental epigenetic transgenerational inheritance and somatic epigenetic mitotic stability.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38Xht1Orsrg%3D&md5=d8c31373318c044f2ab2d04333fd6f1fCAS | 21637037PubMed |

Smallwood, S. A., Tomizawa, S., Krueger, F., Ruf, N., Carli, N., Segonds-Pichon, A., Sato, S., Hata, K., Andrews, S. R., and Kelsey, G. (2011). Dynamic CpG island methylation landscape in oocytes and preimplantation embryos. Nat. Genet. 43, 811–814.
Dynamic CpG island methylation landscape in oocytes and preimplantation embryos.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXotV2ht7g%3D&md5=cc448487b51c385c32396303f8dce0b4CAS | 21706000PubMed |

Smith, Z. D., Chan, M. M., Humm, K. C., Karnik, R., Mekhoubad, S., Regev, A., Eggan, K., and Meissner, A. (2014). DNA methylation dynamics of the human preimplantation embryo. Nature 511, 611–615.
DNA methylation dynamics of the human preimplantation embryo.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXht1ChurfJ&md5=2eeaa2d7b375c64a332d376e37889f84CAS | 25079558PubMed |

Stead, L. M., Au, K. P., Jacobs, R. L., Brosnan, M. E., and Brosnan, J. T. (2001). Methylation demand and homocysteine metabolism: effects of dietary provision of creatine and guanidinoacetate. Am. J. Physiol. Endocrinol. Metab. 281, E1095–E1100.
| 1:CAS:528:DC%2BD3MXos1ahu7Y%3D&md5=1c4e57760f09dd6f03a2bad737d59967CAS | 11595668PubMed |

Steegers-Theunissen, R. P., Twigt, J., Pestinger, V., and Sinclair, K. D. (2013). The periconceptional period, reproduction and long-term health of offspring: the importance of one-carbon metabolism. Hum. Reprod. Update 19, 640–655.
The periconceptional period, reproduction and long-term health of offspring: the importance of one-carbon metabolism.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXhs1GqurnM&md5=2ad85c89624602a89ddf97ff4a456cd3CAS | 23959022PubMed |

Stover, P. J. (2011). Polymorphisms in 1-carbon metabolism, epigenetics and folate-related pathologies. J. Nutrigenet. Nutrigenom. 4, 293–305.
Polymorphisms in 1-carbon metabolism, epigenetics and folate-related pathologies.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XivVGisrY%3D&md5=270caa50c312e1951ad7ed946456a576CAS |

Stover, P. J., and Caudill, M. A. (2008). Genetic and epigenetic contributions to human nutrition and health: managing genome-diet interactions. J. Am. Diet. Assoc. 108, 1480–1487.
Genetic and epigenetic contributions to human nutrition and health: managing genome-diet interactions.Crossref | GoogleScholarGoogle Scholar | 18755320PubMed |

Tanaka, M., Hennebold, J. D., Macfarlane, J., and Adashi, E. Y. (2001). A mammalian oocyte-specific linker histone gene H1oo: homology with the genes for the oocyte-specific cleavage stage histone (cs-H1) of sea urchin and the B4/H1M histone of the frog. Development 128, 655–664.
| 1:CAS:528:DC%2BD3MXit1OitbY%3D&md5=dba73c02c16b1c7db0af7e41545a6b9bCAS | 11171391PubMed |

Tanaka, M., Kihara, M., Hennebold, J. D., Eppig, J. J., Viveiros, M. M., Emery, B. R., Carrell, D. T., Kirkman, N. J., Meczekalski, B., Zhou, J., Bondy, C. A., Becker, M., Schultz, R. M., Misteli, T., De La Fuente, R., King, G. J., and Adashi, E. Y. (2005). H1FOO is coupled to the initiation of oocytic growth. Biol. Reprod. 72, 135–142.
H1FOO is coupled to the initiation of oocytic growth.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXmtlOg&md5=60d1f15a0285430db9a058b9d5d61098CAS | 15371275PubMed |

Torres-Padilla, M. E., Bannister, A. J., Hurd, P. J., Kouzarides, T., and Zernicka-Goetz, M. (2006). Dynamic distribution of the replacement histone variant H3.3 in the mouse oocyte and preimplantation embryos. Int. J. Dev. Biol. 50, 455–461.
Dynamic distribution of the replacement histone variant H3.3 in the mouse oocyte and preimplantation embryos.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XlvVemsbg%3D&md5=ec17c09681ed0dafdf60247cd154aa85CAS | 16586346PubMed |

van der Heijden, G. W., Derijck, A. A., Ramos, L., Giele, M., van der Vlag, J., and de Boer, P. (2006). Transmission of modified nucleosomes from the mouse male germline to the zygote and subsequent remodeling of paternal chromatin. Dev. Biol. 298, 458–469.
Transmission of modified nucleosomes from the mouse male germline to the zygote and subsequent remodeling of paternal chromatin.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XhtVWqurnF&md5=91cce7167f3d27d0bffd9b559b0d7336CAS | 16887113PubMed |

van Engeland, M., Weijenberg, M. P., Roemen, G. M., Brink, M., de Bruine, A. P., Goldbohm, R. A., van den Brandt, P. A., Baylin, S. B., de Goeij, A. F., and Herman, J. G. (2003). Effects of dietary folate and alcohol intake on promoter methylation in sporadic colorectal cancer: the Netherlands cohort study on diet and cancer. Cancer Res. 63, 3133–3137.
| 1:CAS:528:DC%2BD3sXks1eitbk%3D&md5=1680ec53be2e1dd9d74f5f01ceaf9a2fCAS | 12810640PubMed |

Waterland, R. A., and Jirtle, R. L. (2003). Transposable elements: targets for early nutritional effects on epigenetic gene regulation. Mol. Cell. Biol. 23, 5293–5300.
Transposable elements: targets for early nutritional effects on epigenetic gene regulation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXlslGmsrw%3D&md5=73a4f26e9a299c65243370786d67698eCAS | 12861015PubMed |

Waterland, R. A., Dolinoy, D. C., Lin, J. R., Smith, C. A., Shi, X., and Tahiliani, K. G. (2006). Maternal methyl supplements increase offspring DNA methylation at Axin Fused. Genesis 44, 401–406.
Maternal methyl supplements increase offspring DNA methylation at Axin Fused.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XhtVOnsrrM&md5=2c9aadefe29611b5fbf78ecca168bd7dCAS | 16868943PubMed |

Waterland, R. A., Kellermayer, R., Laritsky, E., Rayco-Solon, P., Harris, R. A., Travisano, M., Zhang, W., Torskaya, M. S., Zhang, J., Shen, L., Manary, M. J., and Prentice, A. M. (2010). Season of conception in rural Gambia affects DNA methylation at putative human metastable epialleles. PLoS Genet. 6, e1001252.
Season of conception in rural Gambia affects DNA methylation at putative human metastable epialleles.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXjtlWntg%3D%3D&md5=d04269b0e3e5f53965494e212c918e94CAS | 21203497PubMed |

Watkins, A. J., and Sinclair, K. D. (2014). Paternal low protein diet affects adult offspring cardiovascular and metabolic function in mice. Am. J. Physiol. Heart Circ. Physiol. 306, H1444–H1452.
Paternal low protein diet affects adult offspring cardiovascular and metabolic function in mice.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXptVChsb4%3D&md5=c84036e816b0df0c40628adacc53fa19CAS | 24658019PubMed |

Winter-Vann, A. M., Kamen, B. A., Bergo, M. O., Young, S. G., Melnyk, S., James, S. J., and Casey, P. J. (2003). Targeting Ras signaling through inhibition of carboxyl methylation: an unexpected property of methotrexate. Proc. Natl Acad. Sci. USA 100, 6529–6534.
Targeting Ras signaling through inhibition of carboxyl methylation: an unexpected property of methotrexate.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXktlyhu78%3D&md5=3e0a45b1efc7ae0e4e3df304cfb001b8CAS | 12750467PubMed |

Wolffe, A. P., and Matzke, M. A. (1999). Epigenetics: regulation through repression. Science 286, 481–486.
Epigenetics: regulation through repression.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1MXmvVOht7o%3D&md5=213064d16020f6725cb5beab2ac9e598CAS | 10521337PubMed |

Wykes, S. M., and Krawetz, S. A. (2003). The structural organization of sperm chromatin. J. Biol. Chem. 278, 29 471–29 477.
The structural organization of sperm chromatin.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXlvFOgurs%3D&md5=7f515cb43d408751f13b26a468d5d588CAS |

Yang, M., Gocke, C. B., Luo, X., Borek, D., Tomchick, D. R., Machius, M., Otwinowski, Z., and Yu, H. (2006). Structural basis for CoREST-dependent demethylation of nucleosomes by the human LSD1 histone demethylase. Mol. Cell 23, 377–387.
Structural basis for CoREST-dependent demethylation of nucleosomes by the human LSD1 histone demethylase.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XovVWlu74%3D&md5=6ea4d23efb5a823f1e15216dffbc169aCAS | 16885027PubMed |

Yates, Z., and Lucock, M. (2005). G80A reduced folate carrier SNP modulates cellular uptake of folate and affords protection against thrombosis via a non homocysteine related mechanism. Life Sci. 77, 2735–2742.
G80A reduced folate carrier SNP modulates cellular uptake of folate and affords protection against thrombosis via a non homocysteine related mechanism.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXhtVWit7bP&md5=e3535f292d77abf8c50ae67740fb6482CAS | 15964598PubMed |

Young, L. E., and Beaujean, N. (2004). DNA methylation in the preimplantation embryo: the differing stories of the mouse and sheep. Anim. Reprod. Sci. 82–83, 61–78.
DNA methylation in the preimplantation embryo: the differing stories of the mouse and sheep.Crossref | GoogleScholarGoogle Scholar | 15271444PubMed |

Zhao, R., Russell, R. G., Wang, Y., Liu, L., Gao, F., Kneitz, B., Edelmann, W., and Goldman, I. D. (2001). Rescue of embryonic lethality in reduced folate carrier-deficient mice by maternal folic acid supplementation reveals early neonatal failure of hematopoietic organs. J. Biol. Chem. 276, 10 224–10 228.
Rescue of embryonic lethality in reduced folate carrier-deficient mice by maternal folic acid supplementation reveals early neonatal failure of hematopoietic organs.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXis1Okt74%3D&md5=bd04e77d9675810f134fbd8df9cd6e1aCAS |

Zhao, R., Matherly, L. H., and Goldman, I. D. (2009). Membrane transporters and folate homeostasis: intestinal absorption and transport into systemic compartments and tissues. Expert Rev. Mol. Med. 11, e4.
Membrane transporters and folate homeostasis: intestinal absorption and transport into systemic compartments and tissues.Crossref | GoogleScholarGoogle Scholar | 19173758PubMed |

Zhou, H. R., Zhang, F. F., Ma, Z. Y., Huang, H. W., Jiang, L., Cai, T., Zhu, J. K., Zhang, C., and He, X. J. (2013). Folate polyglutamylation is involved in chromatin silencing by maintaining global DNA methylation and histone H3K9 dimethylation in Arabidopsis. Plant Cell 25, 2545–2559.
Folate polyglutamylation is involved in chromatin silencing by maintaining global DNA methylation and histone H3K9 dimethylation in Arabidopsis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXhsVKksb3K&md5=fad0406f355719ae3ffcce4568a0addeCAS | 23881414PubMed |