Abstract
In this review, we summarize the data on 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine— cytosine modifications which are produced by TET-mediated oxidation of 5-methylcytosine in DNA. We show the biochemistry of modified cytosine, as well as methods for its global and location analysis. We also highlight the milestones in the evolution of ideas on the biological role of 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine in the mammalian genome from their discovery in 2009 to the present time.
Similar content being viewed by others
References
Kriaucionis, S. and Heintz, N., The nuclear DNA base 5-hydroxymethylcytosine is present in Purkinje neurons and the brain, Science, 2009, vol. 324, pp. 929–930. doi 10.1126/science.1169786
Tahiliani, M., Koh, K.P., Shen, Y., et al., Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1, Science, 2009, vol. 324, pp. 930–935. doi 10.1126/science.1170116
He, Y.F., Li, B.Z., Li, Z., et al., Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA, Science, 2011, vol. 333, pp. 1303–1307. doi 10.1126/science.1210944
Maiti, A. and Drohat, A.C., Thymine DNA glycosylase can rapidly excise 5-formylcytosine and 5-carboxylcytosine: Potential implications for active demethylation of CpG sites, J. Biol. Chem., 2011, vol. 286, no. 41, pp. 35334–35338. doi 10.1074/jbc.C111.284620
Efimova, O.A., Pendina, A.A., Tikhonov, A.V., et al., DNA methylation—a major mechanism of human genome reprogramming and regulation, Med. Genet., 2012, vol. 11, no. 4, pp. 10–18.
Kishikawa, S., Murata, T., Ugai, H., et al., Control elements of Dnmt1 gene are regulated in cell-cycle dependent manner, Nucleic Acid Res. Suppl., 2003, vol. 3, pp. 307–309. doi 10.1093/nass/3.1.307
Ko, Y.G., Nishino, K., Hattori, N., et al., Stage-by-stage change in DNA methylation status of Dnmt1 locus during mouse early development, J. Biol. Chem., 2005, vol. 280, no. 10, pp. 9627–9634. doi 10.1074/jbc.M413822200
Trasler, J.M., Alcivar, A.A., Hake, L.E., et al., DNA methyltransferase is developmentally expressed in replicating and non-replicating male germ cells, Nucleic Acid Res., 1992, vol. 20, no. 10, pp. 2541–2545.
Mertineit, C., Yoder, J.A., Taketo, T., et al., Sex-specific exons control DNA methyltransferase in mammalian germ cells, Development, 1998, vol. 125, pp. 889–897.
Chen, T. and Li, E., Establishment and maintenance of DNA methylation patterns in mammals, Curr. Top. Microbiol. Immunol., 2006, vol. 301, pp. 179–201.
Arand, J., Spieler, D., Karius, T., et al., In vivo control of CpG and non-CpG DNA methylation by DNA methyltransferases, PLoS Genet., 2012, vol. 8, no. 6, p. e1002750. doi 10.1371/journal.pgen.1002750
Ramsahoye, B.H., Biniszkiewicz, D., Lyko, F., et al., Non-CpG methylation is prevalent in embryonic stem cells and may be mediated by DNA methyltransferase 3a, Proc. Natl. Acad. Sci. U.S.A., 2000, vol. 97, no. 10, pp. 5237–5242.
Shirane, K., Toh, H., Kobayashi, H., et al., Mouse oocyte methylomes at base resolution reveal genomewide accumulation of non-CpG methylation and role of DNA methyltransferases, PLoS Genet., 2013, vol. 9, p. e1003439. doi 10.1371/journal.pgen.1003439
Watanabe, D., Suetake, I., Tada, T., et al., Stage-and cellspecific expression of Dnmt3a and Dnmt3b during embryogenesis, Mech. Dev., 2002, vol. 118, nos. 1–2, pp. 187–190.
Okano, M., Bell, D.W., Haber, D.A., and Li, E., DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development, Cell, 1999, vol. 99, pp. 247–257.
Kato, Y., Kaneda, M., Hata, K., et al., 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., 2007, vol. 16, pp. 2272–2280. doi 10.1093/hmg/ddm179
Bourc’his, D., Xu, G.L., Lin, C.S., et al., Dnmt3L and the establishment of maternal genomic imprints, Science, 2001, vol. 294, no. 5551, pp. 2536–2539. doi 10.1126/science.1065848
Hata, K., Okano, M., Lei, H., and Li, E., Dnmt3L cooperates with the Dnmt3 family of de novo DNA methyltransferases to establish maternal imprints in mice, Development, 2002, vol. 129, no. 8, pp. 1983–1993.
Turek-Plewa, J. and Jagodzinski, P.P., The role of mammalian DNA methyltransferases in the regulation of gene expression, Cell. Mol. Biol. Lett., 2005, vol. 10, pp. 631–647.
Goll, M.G., Kirpekar, F., Maggert, K.A., et al., Methylation of tRNAAsp by the DNA methyltransferase homolog Dnmt2, Science, 2006, vol. 311, pp. 395–398. doi 10.1126/science.1120976
Zhao, H. and Chen, T., Tet family of 5-methylcytosine dioxygenases in mammalian development, J. Hum. Genet., 2013, vol. 58, no. 7, pp. 421–427. doi 10.1038/jhg.2013.63
Baccarelli, A. and Bollati, V., Epigenetics and environmental chemicals, Curr. Opin. Pediatr., 2009, vol. 21, no. 2, pp. 243–251.
Dickson, K.M., Gustafson, C.B., Young, J.I., et al., Ascorbate-induced generation of 5-hydroxymethylcytosine is unaffected by varying levels of iron and 2-oxoglutarate, Biochem. Biophys. Res. Commun., 2013, vol. 439, pp. 522–527. doi 10.1016/j.bbrc.2013.09.010
Li, W. and Liu, M., Distribution of 5-hydroxymethylcytosine in different human tissues, J. Nucleic Acids, 2011, vol. 2011, p. 870726. doi 10.4061/2011/870726
Gustafson, C.B., Yang, C., Dickson, K.M., et al., Epigenetic reprogramming of melanoma cells by vitamin C treatment, Clin. Epigenet., 2015, vol. 7, p. 51. doi 10.1186/s13148-015-0087-z
Yuan, B.F., 5-methylcytosine and its derivatives, Adv. Clin. Chem., 2014, vol. 67, pp. 151–187. doi 10.1016/bs.acc.2014.09.003
Li, M., Hu, S.L., Shen, Z.J., et al., High-performance capillary electrophoretic method for the quantification of global DNA methylation: Application to methotrexate-resistant cells, Anal. Biochem., 2009, vol. 387, pp. 71–75. doi 10.1016/j.ab.2008.12.033
Fraga, M.F., Uriol, E., Borja Diego, L., et al., Highperformance capillary electrophoretic method for the quantification of 5-methyl 2'-deoxycytidine in genomic DNA: Application to plant, animal and human cancer tissues, Electrophoresis, 2002, vol. 23, pp. 1677–1681. <1677:: AIDELPS1677>3.0.CO;2-Z doi 10.1002/1522-2683(200206)23:11
Stach, D., Schmitz, O.J., Stilgenbauer, S., et al., Capillary electrophoretic analysis of genomic DNA methylation levels, Nucleic Acid Res., 2003, vol. 31, p. E2.
Fraga, M.F., Rodriguez, R., and Canal, M.J., Rapid quantification of DNA methylation by high performance capillary electrophoresis, Electrophores, 2000, vol. 21, pp. 2990–2994. doi 10.1002/1522-2683(20000801)21:14<2990::AID-ELPS2990>3.0.CO;2-I
Zinellu, A., Sotgia, S., De Murtas, V., et al., Evaluation of methylation degree from formalin-fixed paraffinembedded DNA extract by field-amplified sample injection capillary electrophoresis with UV detection, Anal. Bioanal. Chem., 2011, vol. 399, pp. 1181–1186. doi 10.1007/s00216-010-4417-x
Wirtz, M., Stach, D., Kliem, H.C., et al., Determination of the DNA methylation level in tumor cells by capillary electrophoresis and laser-induced fluorescence detection, Electrophoresis, 2004, vol. 25, pp. 839–845. doi 10.1002/elps.200305761
Wang, X., Song, Y., Song, M., et al., Fluorescence polarization combined capillary electrophoresis immunoassay for the sensitive detection of genomic DNA methylation, Anal. Chem., 2009, vol. 81, pp. 7885–7891.
Motorin, Y., Lyko, F., and Helm, M., 5-methylcytosine in RNA: Detection, enzymatic formation and biological functions, Nucleic Acid Res., 2010, vol. 38, pp. 1415–1430. doi 10.1093/nar/gkp1117
Yin, R., Mao, S.Q., Zhao, B., et al., Ascorbic acid enhances tet-mediated 5-methylcytosine oxidation and promotes DNA demethylation in mammals, J. Am. Chem. Soc., 2013, vol. 135, pp. 10396–10403. doi 10.1021/ja4028346
Yang, I., Fortin, M.C., Richardson, J.R., and Buckley, B., Fused-core silica column ultra-performance liquid chromatography-ion trap tandem mass spectrometry for determination of global DNA methylation status, Anal. Biochem., 2011, vol. 409, pp. 138–143. doi 10.1016/j.ab.2010.10.012
Wang, X., Suo, Y., Yin, R., et al., Ultra-performance liquid chromatography/tandem mass spectrometry for accurate quantification of global DNA methylation in human sperms, J. Chromatogr., B Analyt. Technol. Biomed. Life Sci., 2011, vol. 879, pp. 1647–1652. doi 10.1016/j.jchromb.2011.04.002
Kok, R.M., Smith, D.E., Barto, R., et al., Global DNA methylation measured by liquid chromatography-tandem mass spectrometry: Analytical technique, reference values and determinants in healthy subjects, Clin. Chem. Lab. Med., 2007, vol. 45, pp. 903–911. doi 10.1515/CCLM.2007.137
Romerio, A.S., Fiorillo, G., Terruzzi, I., et al., Measurement of DNA methylation using stable isotope dilution and gas chromatography-mass spectrometry, Anal. Biochem., 2005, vol. 336, pp. 158–163. doi 10.1016/j.ab.2004.09.034
Rossella, F., Polledri, E., Bollati, V., et al., Development and validation of a gas chromatography/mass spectrometry method for the assessment, Rapid Commun. Mass Spectrom., 2009, vol. 23, no. 17, pp. 2637–2646. doi 10.1002/rcm.4166
Tang, Y., Gao, X.D., Wang, Y., et al., Widespread existence of cytosine methylation in yeast DNA measured by gas chromatography/mass spectrometry, Anal. Chem., 2012, vol. 84, pp. 7249–7255. doi 10.1021/ac301727c
Leonard, S.A., Wong, S.C., and Nyce, J.W., Quantitation of 5-methylcytosine by onedimensional high-performance thin-layer chromatography, J. Chromatogr., 1993, vol. 645, pp. 189–192.
Barciszewska, M.Z., Barciszewska, A.M., and Rattan, S.I., TLC-based detection of methylated cytosine: Application to aging epigenetics, Biogerontology, 2007, vol. 8, pp. 673–678. doi 10.1007/s10522-007-9109-3
Ito, S., Shen, L., Dai, Q., et al., Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine, Science, 2011, vol. 333, pp. 1300–1303. doi 10.1126/science.1210597
Oakeley, E.J., Schmitt, F., and Jost, J.P., Quantification of 5-methylcytosine in DNA by the chloroacetaldehyde reaction, BioTechniques, 1999, vol. 27, pp. 744–746, 748–750, 752.
Frommer, M., McDonald, L.E., Millar, D.S., et al., A genomic sequencing protocol that yields a positive display of 5-methylcytosine residues in individual DNA strands, Proc. Natl. Acad. Sci. U.S.A., 1992, vol. 89, pp. 1827–1831.
Hu, J., Xing, X., Xu, X., et al., Selective chemical labelling of 5-formylcytosine in DNA by fluorescent dyes, Chemistry, 2013, vol. 19, pp. 5836–5840. doi 10.1002/chem.201300082
Pendina, A.A., Efimova, O.A., Kaminskaya, A.N., et al., Immunocytochemical analysis of human metaphase chromosome methylation status, Tsitologiya, 2005, vol. 47, no. 8, pp. 731–737.
Efimova, O.A., Pendina, A.A., Tikhonov, A.V., et al., A comparative immunocytochemical analysis of DNA methylation patterns in human metaphase chromosomes of adults and fetuses, Mol. Med., 2015, no. 3, pp. 17–21.
Kokalj-Vokac, N., Zagorac, A., Pristovnik, M., et al., DNA methylation of the extraembryonic tissues: An in situ study on human metaphase chromosomes, Chromosome Res., 1998, vol. 6, no. 3, pp. 161–166.
Baranov, V.S., Pendina, A.A., Kuznetsova, T.V., et al., Peculiarities of metaphase chromosome methylation pattern in preimplantation human embryos, Tsitologiya, 2005, vol. 47, no. 8, pp. 723–730.
Pendina, A.A., Efimova, O.A., Fedorova, I.D., et al., DNA methylation patterns of metaphase chromosomes in human preimplantation embryos, Cytogenet. Genome Res., 2011, vol. 132, nos. 1–2, pp. 1–7. doi 10.1159/000318673
Efimova, O.A., Pendina, A.A., Tikhonov, A.V., et al., Chromosome hydroxymethylation patterns in human zygotes and cleavage-stage embryos, Reproduction, 2015, vol. 149, no. 3, pp. 223–233. doi 10.1530/REP-14-0343
Nestor, C., Ruzov, A., Meehan, R., and Dunican, D., Enzymatic approaches and bisulfite sequencing cannot distinguish between 5-methylcytosine and 5-hydroxymethylcytosine in DNA, BioTechniques, 2010, vol. 48, no. 4, pp. 317–319. doi 10.2144/000113403
Kinney, S.M., Chin, H.G., Vaisvila, R., et al., Tissue-specific distribution and dynamic changes of 5-hydroxymethylcytosine in mammalian genomes, J. Biol. Chem., 2011, vol. 286, pp. 24685–24693. doi 10.1074/jbc.M110.217083
Clark, S.J., Harrison, J., Paul, C.L., and Frommer, M., High sensitivity mapping of methylated cytosines, Nucleic Acid Res., 1994, vol. 22, pp. 2990–2997.
Booth, M.J., Branco, M.R., Ficz, G., et al., Quantitative sequencing of 5-methylcytosine and 5-hydroxymethylcytosine at single-base resolution, Science, 2012, vol. 336, pp. 934–937. doi 10.1126/science.1220671
Yu, M., Hon, G.C., Szulwach, K.E., et al., Base-resolution analysis of 5-hydroxymethylcytosine in the mammalian genome, Cell, 2012, vol. 149, pp. 1368–1380.
Booth, M.J., Marsico, G., Bachman, M., et al., Quantitative sequencing of 5-formylcytosine in DNA at single-base resolution, Nat. Chem., 2014, vol. 6, no. 5, pp. 435–440. doi 10.1038/nchem.1893
Thu, K.L., Pikor, L.A., Kennett, J.Y., et al., Methylation analysis by DNA immunoprecipitation, J. Cell. Physiol., 2010, vol. 222, pp. 522–531. doi 10.1002/jcp.22009
Robertson, A.B., Dahl, J.A., and Vagbo, C.B., et al., A novel method for the efficient and selective identification of 5-hydroxymethylcytosine in genomic DNA, Nucleic Acid Res., 2011, vol. 39, p. e55. doi 10.1093/nar/gkr051
Raiber, E.A., Beraldi, D., Ficz, G., et al., Genomewide distribution of 5-formylcytosine in embryonic stem cells is associated with transcription and depends on thymine DNA glycosylase, Genome Biol., 2012, vol. 13, p. R69. doi 10.1186/gb-2012-13-8-r69
Lu, X., Song, C.X., Szulwach, K., et al., Chemical modification-assisted bisulfite sequencing (CABSeq) for 5-carboxylcytosine detection in DNA, J. Am. Chem. Soc., 2013, vol. 135, pp. 9315–9317. doi 10.1021/ja4044856
Korlach, J. and Turner, S.W., Going beyond five bases in DNA sequencing, Curr. Opin. Struct. Biol., 2012, vol. 22, pp. 251–261. doi 10.1016/j.sbi.2012.04.002
Flusberg, B.A., Webster, D.R., Lee, J.H., et al., Direct detection of DNA methylation during singlemolecule, real-time sequencing, Nat. Methods, 2010, vol. 7, pp. 461–465. doi 10.1038/nmeth.1459
Song, C.X., Clark, T.A., and Lu, X.Y., et al., Sensitive and specific single-molecule sequencing of 5-hydroxymethylcytosine, Nat. Methods, 2012, vol. 9, pp. 75–77. doi 10.1038/ncomms1237
Globisch, D., Munzel, M., Muller, M., et al., Tissue distribution of 5-hydroxymethylcytosine and search for active demethylation intermediates, PLoS One, 2010, vol. 5, no. 12, p. e15367. doi 10.1371/journal. pone.0015367
Pfaffeneder, T., Spada, F., Wagner, M., et al., Tet oxidizes thymine to 5-hydroxymethyluracil in mouse embryonic stem cell DNA, Nat. Chem. Biol., 2014, vol. 10, pp. 574–581. doi 10.1038/nchembio.1532
Song, J. and Pfeifer, G.P., Are there specific readers of oxidized 5-methylcytosine bases?, BioEssays, 2016, vol. 38, pp. 1038–1047. doi 10.1002/bies.201600126
Stroud, H., Feng, S., Morey Kinney, S., et al., 5-hydroxymethylcytosine is associated with enhancers and gene bodies in human embryonic stem cells, Genome Biol., 2011, vol. 12, p. R54. doi 10.1186/gb-2011-12-6-r54
Hon, G.C., Song, C.X., Du, T., et al., 5mC oxidation by Tet2 modulates enhancer activity and timing of transcriptome reprogramming during differentiation, Mol. Cell, 2014, vol. 56, pp. 286–297.
Lu, F., Liu, Y., Jiang, L., et al., Role of Tet proteins in enhancer activity and telomere elongation, Genes Dev., 2014, vol. 28, pp. 2103–2119. doi 10.1101/gad.248005.114
Song, C.X., Szulwach, K.E., Dai, Q., et al., Genomewide profiling of 5-formylcytosine reveals its roles in epigenetic priming, Cell, 2013, vol. 153, pp. 678–691. doi 10.1016/j.cell.2013.04.001
Shen, L., Wu, H., Diep, D., et al., Genome-wide analysis reveals TET-and TDG-dependent 5-methylcytosine oxidation dynamics, Cell, 2013, vol. 153, pp. 692–706. doi 10.1016/j.cell.2013.04.002
Williams, K., Christensen, J., and Helin, K., DNA methylation: TET proteins-guardians of CpG islands?, EMBO Rep., 2012, vol. 13, pp. 28–35. doi 10.1038/embor.2011.233
Rauch, T.A., Wu, X., Zhong, X., et al., A human B cell methylome at 100-base pair resolution, Proc. Natl. Acad. Sci. U.S.A., 2009, vol. 106, no. 3, pp. 671–678. doi 10.1073/pnas.0812399106
Song, C.X., Szulwach, K.E., Fu, Y., et al., Selective chemical labeling reveals the genome-wide distribution of 5-hydroxymethylcytosine, Nat. Biotechnol., 2011, vol. 29, pp. 68–72. doi 10.1038/nbt.1732
Spruijt, C.G., Gnerlich, F., Smits, A.H., et al., Dynamic readers for 5-(hydroxy) methylcytosine and its oxidized derivatives, Cell, 2013, vol. 152, pp. 1146–1159. doi 10.1016/j.cell.2013.02.004
Iurlaro, M., Ficz, G., Oxley, D., et al., A screen for hydroxymethylcytosine and formylcytosine binding proteins suggests functions in transcription and chromatin regulation, Genome Biol., 2013, vol. 14, p. R119. doi 10.1186/gb-2013-14-10-r119
Zhou, T., Xiong, J., Wang, M., et al., Structural basis for hydroxymethylcytosine recognition by the SRA domain of UHRF2, Mol. Cell, 2014, vol. 54, pp. 879–886. doi 10.1016/j.molcel.2014.04.003
Iurlaro, M., McInroy, G.R., Burgess, H.E., et al., In vivo genome-wide profiling reveals a tissue-specific role for 5-formylcytosine, Genome Biol., 2016, vol. 17, no. 1, p. 141. doi 10.1186/s13059-016-1001-5
Bachman, M., Uribe-Lewis, S., Yang, X., et al., 5-formylcytosine can be a stable DNA modification in mammals, Nat. Chem. Biol., 2015, vol. 11, pp. 555–557. doi 10.1038/nchembio.1848
Raiber, E.A., Murat, P., Chirgadze, D.Y., et al., 5-formylcytosine alters the structure of the DNA double helix, Nat. Struct. Mol. Biol., 2015, vol. 22, pp. 44–49. doi 10.1038/nsmb.2936
Hashimoto, H., Olanrewaju, Y.O., Zheng, Y., et al., Wilms tumor protein recognizes 5-carboxylcytosine within a specific DNA sequence, Genes Dev., 2014, vol. 28, pp. 2304–2313. doi 10.1101/gad.250746.114
Jin, S.G., Zhang, Z.M., Dunwell, T.L., et al., Tet3 reads 5-carboxylcytosine through its CXXC domain and is a potential guardian against neurodegeneration, Cell Rep., 2016, vol. 14, pp. 493–505. doi 10.1016/j.celrep. 2015.12.044
Wang, L., Zhou, Y., Xu, L., et al., Molecular basis for 5-carboxycytosine recognition by RNA polymerase II elongation complex, Nature, 2015, vol. 523, pp. 621–625. doi 10.1038/nature14482
Hashimoto, H., Zhang, X., and Cheng, X., Activity and crystal structure of human thymine DNA glycosylase mutant N140A with 5-carboxylcytosine DNA at low pH, DNA Repair (Amst)., 2013, vol. 12, pp. 535–540. doi 10.1016/j.dnarep.2013.04.003
Zhang, L., Lu, X., Lu, J., et al., Thymine DNA glycosylase specifically recognizes 5-carboxylcytosine-modified DNA, Nat. Chem. Biol., 2012, vol. 8, pp. 328–330. doi 10.1038/nchembio.914
Xu, Y., Xu, C., Kato, A., et al., Tet3CXXC domain and dioxygenase activity cooperatively regulate key genes for Xenopus eye and neural development, Cell, 2012, vol. 151, pp. 1200–1213. doi 10.1016/j.cell.2012.11.014
Allen, M.D., Grummitt, C.G., Hilcenko, C., et al., Solution structure of the nonmethyl-CpG-binding CXXC domain of the leukaemia-associated MLL histone methyltransferase, EMBO J., 2006, vol. 25, pp. 4503–4512. doi 10.1038/sj.emboj.7601340
Cierpicki, T., Risner, L.E., Grembecka, J., et al., Structure of the MLL CXXC domain-DNA complex and its functional role in MLL-AF9 leukemia, Nat. Struct. Mol. Biol., 2010, vol. 17, pp. 62–68. doi 10.1038/nsmb.1714
Song, J., Rechkoblit, O., Bestor, T.H., and Patel, D.J., Structure of DNMT1-DNA complex reveals a role for autoinhibition in maintenance DNA methylation, Science, 2011, vol. 331, pp. 1036–1040. doi 10.1126/science. 1195380
Xu, C., Bian, C., Lam, R., et al., The structural basis for selective binding of non-methylated CpG islands by the CFP1CXXC domain, Nat. Commun., 2011, vol. 2, p. 227. doi 10.1038/ncomms1237
Branco, M.R., Ficz, G., and Reik, W., Uncovering the role of 5-hydroxymethylcytosine in the epigenome, Nat. Rev. Genet., 2011, vol. 13, pp. 7–13. doi 10.1038/nrg3080
Efimova, O.A., Pendina, A.A., Tikhonov, A.V., et al., Oxidized form of 5-methylcytosine—5-hydroxymethylcytosine: A new insight into the biological significance in the mammalian genome, Russ. J. Genet.: Appl. Res., 2015, vol. 5, pp. 75–81.
Dean, W., DNA methylation and demethylation: A pathway to gametogenesis and development, Mol. Reprod. Dev., 2014, vol. 81, no. 2, pp. 113–125. doi 10.1002/mrd.22280
Amouroux, R., Nashun, B., Shirane, K., et al., De novo DNA methylation drives 5hmC accumulation in mouse zygotes, Nat. Cell. Biol., 2016, vol. 18, no. 2, pp. 225–233.
Author information
Authors and Affiliations
Corresponding author
Additional information
Original Russian Text © O.A. Efimova, A.A. Pendina, A.V. Tikhonov, V.S. Baranov, 2016, published in Ecologicheskaya Genetika, 2016, Vol. 14, No. 4, pp. 14–25.
Rights and permissions
About this article
Cite this article
Efimova, O.A., Pendina, A.A., Tikhonov, A.V. et al. The Evolution of Ideas on the Biological Role of 5-methylcytosine Oxidative Derivatives in the Mammalian Genome. Russ J Genet Appl Res 8, 11–21 (2018). https://doi.org/10.1134/S2079059718010069
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S2079059718010069