Abstract
In this review, we summarize data on 5-hydroxymethylcytosine—a modification of cytosine with a recently discovered epigenetic effect. We discuss the biochemical mechanisms of 5-hydroxymethylcytosine generation and further modification in the mammalian genome, analyze the role of 5-hydroxymethylcytosine in the epigenetic reprogramming during mammalian gametogenesis and early embryogenesis as well as in the regulation of gene expression. We also show recent data on the diseases and the adverse environmental factors, linked to the DNA hydroxymethylation disruptions.
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Al-Mahdawi, S., Sandi, C., Mouro, Pinto, R., and Pook, M.A., PLoS One, 2013, vol. 8, no. 9, p. e74956.
Baranov, V.S., Pendina, A.A., Kuznetsova, T.V., et al., Peculiarities of metaphase chromosome methylation pattern in preimplantation human embryos, Tsitologiia, 2005, vol. 47, no. 8, pp. 723–730.
Beaujean, N., Hartshorne, G., Cavilla, J., et al., Curr. Biol., 2004, vol. 14, pp. R266–R267.
Booth, M.J., Branco, M.R., Ficz, G., et al., Science, 2012, vol. 336, pp. 934–937.
Bradley-Whitman, M.A., and Lovell, M.A., Mech. Ageing Dev., Available online September 3, 2013. doi: pii: S0047-6374 (13)00096-1.10.1016/j.mad.2013.08.005
Carlson, B.M., 4th ed., USA, Mosby, 2009.
Chia, N., Wang, L., Lu, X., Senut, M.C., et al., Epigenetics, 2011, vol. 6, no. 7, pp. 853–856.
Chen, C.C., Wang, K.Y., and Shen, C.K.J., Biol. Chem., 2012, vol. 287, pp. 33116–33121.
Cliffe, L.J., Kieft, R., Southern, T., et al., Nucleic Acids Res., 2009, vol. 37, pp. 1452–1462.
Cortazar, D., Kunz, C., Selfridge, J., et al., Nature, 2011, vol. 470, no. 7334, pp. 419–423.
Cortellino, S., Xu, J., Sannai, M., et al., Cell, 2011, vol. 146, no. 1, pp. 67–79.
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.
Ficz, G., Branco, M.R., Seisenberger, S., et al., Nature, 2011, vol. 473, pp. 398–402.
Fulka, H., Mrazek, M., Tepla, O., and Fulka, J., Jr., Reproduction, 2004, vol. 128, pp. 703–708.
Gambichler, T., Sand, M., and Skrygan, M., Melanoma Res., 2013, vol. 23, no. 3, pp. 218–220.
Gu, T.P., Guo, F., Yang, H., et al., Nature, 2011, vol. 477, no. 7366, pp. 606–610.
Guo, J.U., Su, Y., Zhong, C., et al., Cell, 2011, vol. 145, pp. 423–434.
Hattman, S. and Fukasawa, T., Proc. Natl. Acad. Sci. USA, 1963, vol. 50, pp. 297–300.
He, Y.F., Li, B.Z., Li, Z., et al., Science, 2011, vol. 333, pp. 1303–1307.
Iqbal, K., Jin, S.G., Pfeifer, G.P., and Szabo, P.E., Proc. Natl. Acad. Sci. USA, 2011, vol. 108, no. 9, pp. 3642–3647.
Inoue, A., Shen, L., Dai, Q., He, C., and Zhang, Y., Cell Res., 2011, vol. 21, no. 12, pp. 1670–1676.
Inoue, A. and Zhang, Y., Science, 2011, vol. 334, no. 6053, p. 194.
Ito, S., D’Alessio, A.C., and Taranova, O.V., et al., Nature, 2010, vol. 466, pp. 1129–1133.
Ito, S., Shen, L., Dai, Q., et al., Science, 2011, vol. 333, no. 6047, pp. 1229–1230.
Jäwert, F., Hasseus, B., Kjeller, G., et al., Anticancer Res., 2013, vol. 33, no. 10, pp. 4325–4328.
Jefferson, W.N., Chevalier, D.M., Phelps, J.Y., et al., Mol. Endocrinol., 2013, vol. 27, no. 10, pp. 1666–1677.
Kagiwada, S., Kurimoto, K., Hirota, T., et al., EMBO J., 2012, vol. 32, pp. 340–353.
Kornberg, A., Zimmerman, S.B., Kornberg, S.R., and Josse, J., Proc. Natl. Acad. Sci. USA, 1959, vol. 45, pp. 772–785.
Kothari, R.M. and Shankar, V., J. Mol. Evol., 1976, vol. 7, pp. 325–329.
Kriaucionis, S. and Heintz, N., Science, 2009, vol. 324, pp. 929–930.
Li, W. and Liu, M., J. Nucleic Acids, 2011, vol. 2011, Article ID 870726.
Lian, C.G., Xu, Y., Ceol, C., et al., Cell, 2012, vol. 150, no. 6, pp. 1135–1146.
Liu, C., Liu, L., Chen, X., et al., PLoS One, 2013, vol. 8, no. 5, p. e62828.
Maiti, A., and Drohat, A.C., J. Biol. Chem., 2011, vol. 286, no. 41, pp. 35334–35338.
Nakamura, T., Arai, Y., Umehara, H., et al., Nature Cell Biol., 2007, vol. 9, no. 1, pp. 64–71.
Nakamura, T., Liu, Y.J., Nakashima, H., et al., Nature, 2012, vol. 486, no. 7403, pp. 415–419.
Nestor, C.E., Ottaviano, R., Reddington, J., et al., Genome Res., 2012, vol. 22, no. 3, pp. 467–477.
Pastor, W.A., Pape, U.J., Huang, Y., et al., Nature, 2011, vol. 473, pp. 394–397.
Pendina, A.A., Efimova, O.A., Kaminskaia, A.N., et al., Immunocytochemical analysis of human metaphase chromosome methylation status, Tsitologiia, 2005, vol. 47, no. 8, pp. 731–737.
Pendina, A.A., Efimova, O.A., Fedorova, I.D., et al., Cytogenet. Genome Res., 2011, vol. 132, nos. 1–2, pp. 1–7.
Penn, N.W., Suwalski, R., O’Riley, C., et al., Biochem. J., 1972, vol. 126, pp. 781–790.
Pfaffeneder, T., Hackner, B., Truss, M., et al., Angew. Chem., Int. Ed. Engl., 2011, vol. 50, no. 31, pp. 7008–7012.
Salvaing, J., Aguirre-Lavin, T., Boulesteix, C., et al., PLoS One, 2012, vol. 7, no. 5, p. e38156.
Shedlovsky, A. and Brenner, S., Proc. Natl. Acad. Sci. USA, 1963, vol. 50, pp. 300–305.
Shen, L. and Zhang, Y., Curr. Opin. Cell Biol., 2013, vol. 25, no. 3, pp. 289–296.
Someya, S., Yu, W., Hallows, W.C., et al., Cell, 2010, vol. 143, no. 5, pp. 802–812.
Song, C.X., Szulwach, K.E., Fu, Y., et al., Nat. Biotechnol., 2011, vol. 29, pp. 68–72.
Song, C.X. and He, C., Genome Biol., 2012, vol. 13, p. 173.
Steinberg, J.J., Cajigas, A., and Brownlee, M.J., Chromatographia, 1992, vol. 574, pp. 41–55.
Stroud, H., Feng, S., Morey, Kinney S., et al., Genome Biol., 2011, vol. 12, p. R54.
Szulwach, K.E., Li, X., Li, Y., et al., Nat. Neurosci., 2011a, vol. 14, pp. 1607–1616.
Szulwach, K.E., Li, X., Li, Y., et al., PLoS Genet., 2011b, vol. 7, no. 6, p. e1002154.
Tahiliani, M., Koh, K.P., Shen, Y., et al., Science, 2009, vol. 324, pp. 930–935.
Thomson, J.P., Lempiainen, H., Hackett, J.A., et al., Genome Biol., 2012, vol. 13, p. R93.
Valinluck, V. and Sowers, L.C., Cancer Res., 2007, vol. 67, pp. 946–950.
Wang, T., Pan, Q., Lin, L., et al., Hum. Mol. Genet., 2012, vol. 21, pp. 5500–5510.
Yang, Y., Lin, X., Wang, J.Q., et al., Hum. Mol. Genet., 2013, vol. 22, no. 18, pp. 3641–3653.
Williams, K., Christensen, J., Pedersen, M.T., et al., Nature, 2011, vol. 473, pp. 343–348.
Wossidlo, M., Arand, J., Sebastiano, V., et al., EMBO J., 2010, vol. 29, no. 11, pp. 1877–1888.
Wossidlo, M., Nakamura, T., Lepikhov, K., et al., Nat. Commun., 2011, vol. 2, p. 241.
Wu, H., D’Alessio, A.C., Ito, S., et al., Genes Dev., 2011, vol. 25, pp. 679–684.
Wyatt, G.R. and Cohen, S.S., Nature, 1952, vol. 170, pp. 1072–1073.
Xu, Y., Zhang, J.J., Grifo, J.A., and Krey, L.C., Mol. Human Reprod., 2005, vol. 11, no. 3, pp. 167–171.
Xu, Y., Wu, F., Tan, L., et al., Mol. Cell, 2011, vol. 42, pp. 451–464.
Yamaguchi, S., Hong, K., Liu, R., et al., Nature, 2012, vol. 492, pp. 443–447.
Yamaguchi, S., Hong, K., Liu, R., et al., Cell Res., 2013, vol. 23, no. 3, pp. 329–339.
Yang, H., Liu, Y., Bai, F., et al., Oncogene, 2013, vol. 32, no. 5, pp. 663–669.
Yu, Z., Genest, P.A., Riet, B., et al., Nucleic Acids Res., 2007, vol. 35, pp. 2107–2115.
Yu, M., Hon, G.C., Szulwach, K.E., et al., Cell, 2012, vol. 149, pp. 1368–1380.
Zhu, B., Zheng, Y., Angliker, H., et al., Nucleic Acids Res., 2000, vol. 28, no. 21, pp. 4157–4165.
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Original Russian Text © O.A. Efimova, A.A. Pendina, A.V. Tikhonov, T.V. Kuznetzova, V.S. Baranov, 2014, published in Ekologicheskaya Genetika, 2014, Vol. 12, No. 1, pp. 3–13.
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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 5, 75–81 (2015). https://doi.org/10.1134/S2079059715020033
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DOI: https://doi.org/10.1134/S2079059715020033