DNA methyltransferase 1 mutations and mitochondrial pathology: Is mtDNA methylated?

Frontiers in Genetics

Volumn 5, Issue FEB, 2015, Pages

  Maresca, Alessandra ^a   Zaffagnini, Mirko ^b   Caporali, Leonardo ^c   Carelli, Valerio ^a,c   Zanna, Claudia ^b  

^a UNIVERSITY OF BOLOGNA   (Italy)

^b UNIVERSITY OF BOLOGNA   (Italy)

^c BELLARIA HOSPITAL   (Italy)

Author keywords

ADCA DN; DNMT1 mutations; HSN1E; Mitochondrial dysfunction; mtDNA methylation

Indexed keywords

5 METHYLCYTOSINE; DNA METHYLTRANSFERASE 1; DNA METHYLTRANSFERASE 2; DNA METHYLTRANSFERASE 3A; DNA METHYLTRANSFERASE 3B; METHYLTRANSFERASE; MITOCHONDRIAL DNA; UNCLASSIFIED DRUG;

ARTICLE; CEREBELLAR ATAXIA; DEMENTIA; DISORDERS OF MITOCHONDRIAL FUNCTIONS; DNA METHYLATION; GENE EXPRESSION; GENE MUTATION; HEARING IMPAIRMENT; HUMAN; NARCOLEPSY; NEUROLOGIC DISEASE; NEUROPATHY;

EID: 84923563998     PISSN: None     EISSN: 16648021     Source Type: Journal    
DOI: 10.3389/fgene.2015.00090     Document Type: Article

References (157)

1. Akalin, A., Garrett-Bakelman, F.E., Kormaksson, M., Busuttil, J., Zhang, L., Khrebtukova, I., et al., (2012), Base-pair resolution DNA methylation sequencing reveals profoundly divergent epigenetic landscapes in acute myeloid leukemia. PLoS Genet. 8, e1002781. doi:10.1371/journal.pgen.1002781.
2. Ansari, R., Mahta, A., Mallack, E., and Luo, J.J., (2014), Hyperhomocysteinemia and neurologic disorders: a review. J Clin Neurol. 10, 281-288. doi:10.3988/jcn.2014.10.4.281.
3. Arand, J., Spieler, D., Karius, T., Branco, M.R., Meilinger, D., Meissner, A. et al., (2012). In vivo control of CpG and non-CpG DNA methylation by DNA methyltransferases, PLoS Genet. 8, e1002750. doi:10.1371/journal.pgen.1002750.
4. Bakulski, K.M., Dolinoy, D.C., Sartor, M.A., Paulson,H.L., Konen,J.R., Lieberman, A.P., et al., (2012), Genome-wide DNA methylation differences between late-onset Alzheimer's disease and cognitively normal controls in human frontal cortex. J. Alzheimers Dis. 29, 571-588. doi:10.3233/JAD-2012- 111223.
5. Bashtrykov, P., Jankevicius, G., Smarandache, A., Jurkowska, R.Z., Ragozin, S., and Jeltsch, A., (2012), Specificity of Dnmt1 for methylation of hemimethylated CpG sites resides in its catalytic domain. Chem Biol. 19, 572-578. doi:10.1016/j.chembiol.2012.03.010.
6. Bashtrykov, P., Rajavelu, A., Hackner, B., Ragozin, S., Carell, T., and Jeltsch, A., (2014), Targeted mutagenesis results in an activation of DNA methyltransferase 1 and confirms an autoinhibitory role of its RFTS domain. Chembiochem. 15, 743-748. doi:10.1002/cbic.201300740.
7. Bellizzi, D., D'Aquila, P., Scafone, T., Giordano, M., Riso, V., Riccio, A., and Passarino, G., (2013), The Control Region of Mitochondrial DNA Shows an Unusual CpG and Non-CpG Methylation Pattern. DNA Res. 20, 537-547. doi:10.1093/dnares/dst029.
8. Bestor, T.H., (2000), The DNA methyltransferases of mammals. Hum Mol Genet. 9, 2395-2402.
9. Bogenhagen, D.F., (2012), Mitochondrial DNA nucleoid structure. Biochim Biophys Acta. 1819, 914-920. doi:10.1016/j.bbagrm.2011.11.005.
10. Burté, F., Carelli, V., Chinnery, P.F., and Yu-Wai-Man, P., (2014), Disturbed mitochondrial dynamics and neurodegenerative disorders. Nat Rev Neurol. Dec 9. doi:10.1038/nrneurol.2014.228.
11. Byun, H.M., Panni, T., Motta, V., Hou, L., Nordio, F., Apostoli, P., et al., (2013), Effects of airborne pollutants on mitochondrial DNA methylation. Part Fibre Toxicol. 10, 18. doi:10.1186/1743-8977-10-18.
12. Campbell, C.T., Kolesar, J.E., and Kaufman, B.A., (2012), Mitochondrial transcription factor A regulates mitochondrial transcription initiation, DNA packaging, and genome copy number. Biochim Biophys Acta. 1819, 921-929. doi:10.1016/j.bbagrm.2012.03.002.
13. Cardon, L.R., Burge, C., Clayton, D.A., and Karlin, S., (1994), Pervasive CpG suppression in animal mitochondrial genomes. Proc Natl Acad Sci U S A. 91, 3799-3803.
14. Cedar, H., and Bergman, Y., (2011), Epigenetics of haematopoietic cell development. Nat Rev Immunol. 11, 478-488. doi:10.1038/nri2991.
15. Chatterjee, R., and Vinson, C., (2012), CpG methylation recruits sequence specific transcription factors essential for tissue specific gene expression. Biochim Biophys Acta.1819, 763-770. doi:10.1016/j.bbagrm.2012.02.014.
16. Chen, R.Z., Pettersson, U., Beard, C., Jackson-Grusby, L., and Jaenisch, R., (1998), DNA hypomethylation leads to elevated mutation rates. Nature 395, 89-93.
17. Chen, T., and Li, E., (2006), Establishment and maintenance of DNA methylation patterns in mammals. Curr Top Microbiol Immunol. 301:179-201.
18. Chen, T., Hevi, S., Gay, F., Tsujimoto, N., He, T., Zhang, B., et al., (2007), Complete inactivation of DNMT1 leads to mitotic catastrophe in human cancer cells. Nat Genet. 39, 391-396.
19. Chen, T., Tsujimoto, N., and Li, E., (2004), The PWWP domain of Dnmt3a and Dnmt3b is required for directing DNA methylation to the major satellite repeats at pericentric heterochromatin. Mol Cell Biol. 24, 9048-9058.
20. Chen, T., Ueda, Y., Dodge, J.E., Wang, Z., and Li, E., (2003), Establishment and maintenance of genomic methylation patterns in mouse embryonic stem cells by Dnmt3a and Dnmt3b. Mol Cell Biol. 23, 5594-5605.
21. Cheng, X., (1995), Structure and function of DNA methyltransferases. Annu Rev Biophys Biomol Struct. 24, 293-318.
22. Cheng, X., and Blumenthal, R.M., (2008), Mammalian DNA methyltransferases: a structural perspective. Structure 16, 341-50. doi:10.1016/j.str.2008.01.004.
23. Chestnut, B.A., Chang, Q,. Price, A., Lesuisse, C., Wong, M., and Martin, L.J., (2011), Epigenetic regulation of motor neuron cell death through DNA methylation. J Neurosci. 31, 16619-16636. doi:10.1523/JNEUROSCI.1639-11.2011.
24. Chouliaras, L., Mastroeni, D., Delvaux, E., Grover, A., Kenis, G., Hof, P.R., et al., (2013), Consistent decrease in global DNA methylation and hydroxymethylation in the hippocampus of Alzheimer's disease patients. Neurobiol Aging. 34, 2091-2099. doi:10.1016/j.neurobiolaging.2013.02.021.
25. Coppieters, N., Dieriks, B.V., Lill, C., Faull, R.L., Curtis, M.A., Dragunow, M., (2014), Global changes in DNA methylation and hydroxymethylation in Alzheimer's disease human brain. Neurobiol Aging. 35, 1334-1344. doi:10.1016/j.neurobiolaging.2013.11.031.
26. Cozzolino, M., Ferri, A., Valle, C., and Carrì, M.T., (2013), Mitochondria and ALS: implications from novel genes and pathways. Mol Cell Neurosci. 55, 44-49. doi:10.1016/j.mcn.2012.06.001.
27. Dawid, I.B., (1974), 5-methylcytidylic acid: absence from mitochondrial DNA of frogs and HeLa cells. Science 184, 80-81.
28. Denis, H., Ndlovu, M.N., and Fuks, F., (2011), Regulation of mammalian DNA methyltransferases: a route to new mechanisms. EMBO Rep. 12, 647-656. doi.org/10.1038/embor.2011.11.
29. Desplats, P., Spencer, B., Coffee, E., Patel, P., Michael, S., Patrick, C., et al., (2011), Alpha synuclein sequesters Dnmt1 from the nucleus: a novel mechanism for epigenetic alterations in Lewy body diseases. J Biol Chem. 286, 9031-9037. doi:10.1074/jbc.C110.212589.
30. Dhayalan, A., Rajavelu, A., Rathert, P., Tamas, R., Jurkowska, R.Z., Ragozin, S., and Jeltsch, A., (2010), The Dnmt3a PWWP domain reads histone 3 lysine 36 trimethylation and guides DNA methylation. J Biol Chem. 285, 26114-26120. doi:10.1074/jbc.M109.089433.
31. Dhe-Paganon, S., Syeda, F., and Park, L., (2011), DNA methyl transferase 1: regulatory mechanisms and implications in health and disease. Int J Biochem Mol Biol. 2, 58-66.
32. Ding, F., and Chaillet, J.R., (2002), In vivo stabilization of the Dnmt1 (cytosine-5)- methyltransferase protein. Proc Natl Acad Sci U S A. 99, 14861-14866.
33. Dodge, J.E., Okano, M., Dick, F., Tsujimoto, N., Chen, T., Wang, S., et al., (2005), Inactivation of Dnmt3b in mouse embryonic fibroblasts results in DNA hypomethylation, chromosomal instability, and spontaneous immortalization. J Biol Chem. 280, 17986-17991.
34. Dong, A., Yoder, J.A., Zhang, X., Zhou, L., Bestor, T.H., and Cheng, X., (2001), Structure of human DNMT2, an enigmatic DNA methyltransferase homolog that displays denaturant resistant binding to DNA. Nucleic Acids Res. 29, 439-448.
35. Dzitoyeva, S., Chen, H., and Manev, H., (2012), Effect of aging on 5-hydroxymethylcytosine in brain mitochondria. Neurobiol Aging. 33, 2881-2891. doi:10.1016/j.neurobiolaging.2012.02.006.
36. Easwaran, H.P., Schermelleh, L., Leonhardt, H., and Cardoso, M.C., (2008), Replication independent chromatin loading of Dnmt1 during G2 and M phases. EMBO Rep. 5, 1181-1186.
37. Esteller, M., (2008), Epigenetics in cancer. N Engl J Med 358, 1148-1159. doi:10.1056/NEJMra072067.
38. Farge, G., Mehmedovic, M., Baclayon, M., van den Wildenberg, S.M., Roos, W.H., Gustafsson, C.M., et al., (2014), In vitro-reconstituted nucleoids can block mitochondrial DNA replication and transcription. Cell Rep. 8, 66-74. doi:10.1016/j.celrep.2014.05.046.
39. Fatemi, M., Hermann, A., Gowher, H., and Jeltsch, A., (2002), Dnmt3a and Dnmt1 functionally cooperate during de novo methylation of DNA. Eur J Biochem. 269, 4981-4984.
40. Feinberg, A.P., (2007), Phenotypic plasticity and the epigenetics of human disease. Nature 447, 433-440. doi:10.1038/nature05919.
41. Fellinger, K., Rothbauer, U., Felle, M., Längst, G., and Leonhardt, H., (2009), Dimerization of DNA methyltransferase 1 is mediated by its regulatory domain. J Cell Biochem. 106, 521-528. doi:10.1002/jcb.22071.
42. Fontana, A., Gast, H., Reith, W., Recher, M., Birchler, T., and Bassetti, C.L., (2010), Narcolepsy: autoimmunity, effector T cell activation due to infection, or T cell independent, major histocompatibility complex class II induced neuronal loss? Brain 133, 1300-1311.
43. Forbes, S.A., Bhamra, G., Bamford, S., Dawson, E., Kok, C., Clements, J., et al., (2008), The Catalogue of Somatic Mutations in Cancer (COSMIC). Curr Protoc Hum Genet. Chapter 10, Unit 10.11. doi:10.1002/0471142905.hg1011s57.
44. Ghosh, S., Sengupta, S., and Scaria, V., (2014), Comparative analysis of human mitochondrial methylomes shows distinct patterns of epigenetic regulation in mitochondria. Mitochondrion 18, 58-62. doi:10.1016/j.mito.2014.07.007.
45. Goll, M.G., Kirpekar, F., Maggert, K.A., Yoder, J.A., Hsieh, C.L., Zhang, X., et al., (2006), Methylation of tRNAAsp by the DNA methyltransferase homolog Dnmt2. Science 311, 395-398. doi:10.1126/science.1120976.
46. Goyal, R., Reinhardt, R., and Jeltsch, A., (2006), Accuracy of DNA methylation pattern preservation by the Dnmt1 methyltransferase. Nucleic Acids Res. 34, 1182-1188.
47. Guo, J.U., Su, Y., Shin, J.H., Shin, J., Li, H., Xie, B., et al., (2014), Distribution, recognition and regulation of non-CpG methylation in the adult mammalian brain. Nat Neurosci. 17, 215-222. doi:10.1038/nn.3607.
48. Hata, K., Okano, M., Lei, H., and Li, E., (2002), Dnmt3L cooperates with the Dnmt3 family of de novo DNA methyltransferases to establish maternal imprints in mice. Development 129, 1983- 1993.
49. Hermann, A., Goyal, R., and 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.
50. Hermann, A., Schmitt, S., and Jeltsch, A., (2003), The human Dnmt2 has residual DNA-(cytosine- C5) methyltransferase activity. J Biol Chem. 278, 31717-31721. doi:10.1074/jbc.M305448200.
51. Hojo, K., Imamura, T., Takanashi, M., Ishii, K., Sasaki, M., Imura, S., et al., (1999), Hereditary sensory neuropathy with deafness and dementia: a clinical and neuroimaging study. Eur J Neurol. 6, 357-361.
52. Holliday, R., and Pugh, J.E., (1975), DNA modification mechanisms and gene activity during development. Science 187, 226-232.
53. Hong, E.E., Okitsu, C.Y., Smith, A.D., and Hsieh, C.L., (2013), Regionally specific and genome wide analyses conclusively demonstrate the absence of CpG methylation in human mitochondrial DNA. Mol Cell Biol. 33, 2683-2690. doi:10.1128/MCB.00220-13.
54. Hor, H., Bartesaghi, L., Kutalik, Z., Vicário, J.L., de Andrés, C., Pfister, C., et al., (2011), A missense mutation in myelin oligodendrocyte glycoprotein as a cause of familial narcolepsy with cataplexy. Am J Hum Genet. 89, 474-479. doi:10.1016/j.ajhg.2011.08.007. Erratum in: Am J Hum Genet. 2012, 91(2), 396.
55. Howard, G., Eiges, R., Gaudet, F., Jaenisch, R., and Eden, A., (2008), Activation and transposition of endogenous retroviral elements in hypomethylation induced tumors in mice. Oncogene 27, 404-408. doi:10.1038/sj.onc.1210631.
56. Iacobazzi, V., Castegna, A., Infantino, V., and Andria, G., (2013), Mitochondrial DNA methylation as a next-generation biomarker and diagnostic tool. Mol Genet Metab. 110, 25-34. doi:10.1016/j.ymgme.2013.07.012.
57. Iacobuzio-Donahue, C.A., (2009), Epigenetic changes in cancer. Annu Rev Pathol. 4, 229-249. doi:10.1146/annurev.pathol.3.121806.151442.
58. Infantino, V., Castegna, A., Iacobazzi, F., Spera, I., Scala, I., Andria, G., and Iacobazzi, V., (2011), Impairment of methyl cycle affects mitochondrial methyl availability and glutathione level in Down's syndrome. Mol Genet Metab. 102, 378-382.
59. Ishida, M.I., and Moore, G.E., (2013), The role of imprinted genes in humans. Molecular Aspects of Medicine 34, 826-840. doi:10.1016/j.mam.2012.06.009.
60. Jakovcevski, M., and Akbarian, S., (2012), Epigenetic mechanisms in neurodevelopmental and neurodegenerative disease. Nat Med. 18, 1194-1204. doi:10.1038/nm.2828.
61. Jeltsch, A., (2002), Beyond Watson and Crick: DNA methylation and molecular enzymology of DNA methyltransferases. Chembiochem. 3, 274-293. Erratum in: Chembiochem 2002 May 3; 3, 382.
62. Jeltsch, A., (2006), Molecular enzymology of mammalian DNA methyltransferases. Curr Top Microbiol Immunol. 301, 203-225.
63. Jeltsch, A., and Jurkowska, R.Z., (2014), New concepts in DNA methylation. Trends Biochem Sci. 39, 310-318. doi:10.1016/j.tibs.2014.05.002.
64. Jia, D., Jurkowska, R.Z., Zhang, X., Jeltsch, A., and Cheng, X., (2007), Structure of Dnmt3a bound to Dnmt3L suggests a model for de novo DNA methylation. Nature 449, 248-251.
65. Jones, P.A., and Baylin, S.B., (2007), The Epigenomics of Cancer. Cell 128, 683-692. doi:10.1016/j.cell.2007.01.029.
66. Jones, P.A., and Liang, G., (2009), Rethinking how DNA methylation patterns are maintained. Nat Rev Genet. 10, 805-811. doi.org/10.1038/nrg2651.
67. Jowaed, A., Schmitt, I., Kaut, O., and Wüllner, U., (2010), Methylation regulates alpha-synuclein expression and is decreased in Parkinson's disease patients' brains. J Neurosci. 30, 6355-6359. doi:10.1523/JNEUROSCI.6119-09.2010.
68. Jurkowska, R.Z., Jurkowski, T.P., and Jeltsch, A., (2011a), Structure and function of mammalian DNA methyltransferases. Chembiochem. 12, 206-222. doi:10.1002/cbic.201000195.
69. Jurkowska, R.Z., Rajavelu, A., Anspach, N., Urbanke, C., Jankevicius, G., Ragozin, S., et al., (2011b), Oligomerization and binding of the Dnmt3a DNA methyltransferase to parallel DNA molecules: heterochromatic localization and role of Dnmt3L. J Biol Chem. 286, 24200-24207. doi:10.1074/jbc.M111.254987.
70. Jurkowski, T.P., Meusburger, M., Phalke, S., Helm, M., Nellen, W., Reuter, G., and Jeltsch, A., (2008), Human DNMT2 methylates tRNA(Asp) molecules using a DNA methyltransferase-like catalytic mechanism. RNA 14,1663-1670. doi:10.1261/rna.970408.
71. Kaneda, M., Okano, M., Hata, K., Sado, T., Tsujimoto, N., Li, E., and Sasaki, H., (2004), Essential role for de novo DNA methyltransferase Dnmt3a in paternal and maternal imprinting. Nature 429, 900-903.
72. Kanherkar, R.R., Bhatia-Dey, N., and Csoka, A.B., (2014a), Epigenetics across the human lifespan. Front Cell Dev Biol. 2:49. doi:10.3389/fcell.2014.00049.
73. Kanherkar, R.R., Bhatia-Dey, N., Makarev, E., and Csoka, A.B., (2014b), Cellular reprogramming for understanding and treating human disease. Front Cell Dev Biol. 2:67. doi:10.3389/fcell.2014.00067.
74. Kar, S., Deb, M., Sengupra, D., Shilpi, A., Parbin, S., Torrisani, J., et al., (2012), An insight into the various regulatory mechanisms modulating human DNA methyltransferase 1 stability and function. Epigenetics 9, 994-1007.
75. Kelly, R.D., Mahmud, A., McKenzie, M., Trounce, I.A., and St John, J.C., (2012), Mitochondrial DNA copy number is regulated in a tissue specific manner by DNA methylation of the nuclear encoded DNA polymerase gamma A. Nucleic Acids Res. 40, 10124-10138. doi:10.1093/nar/gks770.
76. Kimura, F., Seifert, H.H., Florl, A.R., Santourlidis, S., Steinhoff, C., Swiatkowski, S., et al., (2003), Decrease of DNA methyltransferase 1 expression relative to cell proliferation in transitional cell carcinoma. Int J Cancer. 104, 568-578.
77. Klein, C.J., Bird, T., Ertekin-Taner, N., Lincoln, S., Hjorth, R., Wu Y., et al., (2013), DNMT1 mutation hot spot causes varied phenotypes of HSAN1 with dementia and hearing loss. Neurology 80, 824-828. doi:10.1212/WNL.0b013e318284076d.
78. Klein, C.J., Botuyan, M.V., Wu Y., Ward, C.J., Nicholson, G.A., Hammans, S., et al., (2011), Mutations in DNMT1 cause hereditary sensory neuropathy with dementia and hearing loss. Nat Genet., 43, 595-600.
79. Kohli, R.M., and Zhang, Y., (2013), TET enzymes, TDG and the dynamics of DNA demethylation. Nature 502, 472-479. doi:10.1038/nature12750.
80. Kondilis-Mangum, H.D., and Wade, P.A., (2012), Epigenetics and the adaptive immune response. Mol Aspects Med. 34, 813-825. doi:10.1016/j.mam.2012.06.008.
81. Kornum, B.R., Kawashima, M., Faraco, J., Lin, L., Rico, T.J., Hesselson, S., et al., (2011) Common variants in P2RY11 are associated with narcolepsy. Nat Genet. 43, 66-71. doi: 10.1038/ng.734.
82. Krishnakumar, R., and Blelloch, R.H., (2013), Epigenetics of cellular reprogramming. Curr Opin Genet Dev. 23, 548-555. doi: 10.1016/j.gde.2013.06.005.
83. Landan, G., Cohen, N.M., Mukamel, Z., Bar, A., Molchadsky, A., Brosh, R., et al., (2012), Epigenetic polymorphism and the stochastic formation of differentially methylated regions in normal and cancerous tissues. Nat Genet. 44, 1207-1214. doi:10.1038/ng.2442.
84. Lande-Diner, L., Zhang, J., Ben-Porath, I., Amariglio, N., Keshet, I., Hecht, M., et al., (2007), Role of DNA methylation in stable gene repression. J Biol Chem. 282, 12194-12200.
85. Lascaro, D., Castellana, S., Gasparre, G., Romeo, G., S accone, C., and Attimonelli, M., (2008), The RHNumtS compilation: features and bioinformatics approaches to locate and quantify Human NumtS. BMC Genomics 9, 267. doi:10.1186/1471-2164-9-267.
86. Lashley, T., Gami, P., Valizadeh, N., Li, A., Revesz, T., and Balazs, R., (2014), Alterations in global DNA methylation and hydroxymethylation are not detected in Alzheimer's disease. Neuropathol Appl Neurobiol. Sep 9.
87. Laurent, L., Wong, E., Li, G., Huynh, T., Tsirigos, A., Ong, C.T., et al., (2010), Dynamic changes in the human methylome during differentiation. Genome Res. 20, 320-331. doi:10.1101/gr.101907.109
88. Lee, P.P., Fitzpatrick, D.R., Beard, C., Jessup, H.K., Lehar, S., Makar, K.W., et al., (2001), A critical role for Dnmt1 and DNA methylation in T cell development, function, and survival. Immunity 15, 763-774.
89. Lee, T., Zhai, J., and Meyers, B.C., (2010), Conservation and divergence in eukaryotic DNA methylation. PNAS 107, 9027-9028.
90. Leonhardt, H., Page, A.W., Weier, H.U., and Bestor, T.H., (1992), A targeting sequence directs DNA methyltransferase to sites of DNA replication in mammalian nuclei. Cell 71, 865-873.
91. Li, E., Bestor, T.H., and Jaenisch, R., (1992), Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell 69, 915-926.
92. Li, G., Zan, H., Xu, Z., and Casali, P., (2013), Epigenetics of the antibody response. Trends Immunol. 34, 460-470. doi:10.1016/j.it.2013.03.006.
93. Loughery, J.E., Dunne, P.D., O'Neill, K.M., Meehan, R.R., McDaid, J.R., and Walsh, C.P., (2011), DNMT1 deficiency triggers mismatch repair defects in human cells through depletion of repair protein levels in a process involving the DNA damage response. Hum Mol Genet. 20, 3241- 3255. doi:10.1093/hmg/ddr236.
94. Lu, H., Liu, X., Deng, Y., and Qing, H., (2013), DNA methylation, a hand behind neurodegenerative diseases. Front Aging Neurosci. 5:85. doi:10.3389/fnagi.2013.00085.
95. Maekawa, M., Taniguchi, T., Higashi, H., Sugimura, H., Sugano, K., and Kanno, T., (2004), Methylation of mitochondrial DNA is not a useful marker for cancer detection. Clin Chem. 2004 50, 1480-1481.
96. Mastroeni, D., McKee, A., Grover, A., Rogers, J., Coleman, P.D., (2009), Epigenetic differences in cortical neurons from a pair of monozygotic twins discordant for Alzheimer's disease. PLoS One. 4, e6617. doi:10.1371/journal.pone.0006617.
97. Matsumoto, L., Takuma, H., Tamaoka, A., Kurisaki, H., Date, H., Tsuji, S., and Iwata, A., (2010), CpG demethylation enhances alpha-synuclein expression and affects the pathogenesis of Parkinson's disease. PLoS One 5, e15522. doi:10.1371/journal.pone.0015522.
98. Melberg, A., Hetta, J., Dahl, N., Nennesmo, I., Bengtsson, M., Wibom, R., et al., (1995), Autosomal dominant cerebellar ataxia deafness and narcolepsy. J Neurol Sci. 134, 119-129.
99. Moghadam, K.K., Pizza, F., La Morgia, C., Franceschini, C., Tonon, C., Lodi, R., et al., (2014), Narcolepsy is a common phenotype in HSAN IE and ADCA-DN. Brain 137, 1643-1655.
100. Mortusewicz, O., Schermelleh, L., Walter, J., Cardoso, M.C., and Leonhardt, H., (2005), Recruitment of DNA methyltransferase I to DNA repair sites. Proc Natl Acad Sci U S A. 102, 8905-8909.
101. Nass, M.M., (1973), Differential methylation of mitochondrial and nuclear DNA in cultured mouse, hamster and virus-transformed hamster cells. In vivo and in vitro methylation. J Mol Biol. 80, 155-175.
102. O'Keefe, R.T., Henderson, S.C., and Spector, D .L., (1992), Dynamic organization of DNA replication in mammalian cell nuclei: spatially and temporally defined replication of chromosome-specific alpha-satellite DNA sequences. J Cell Biol. 116, 1095-1110.
103. Okano, M., Bell, D.W., Haber, D.A. and Li,E., (1999), DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 99, 247-257.
104. Okano, M., Xie, S., and Li, E. (1998), Cloning and characterization of a family of novel mammalian DNA (cytosine-5) methyltransferases. Nat Genet. 19, 219-220. doi:10.1038/890.
105. Ooi, S.K., Qiu, C., Bernstein, E., Li, K., Jia, D., Yang, Z., et al., (2007), DNMT3L connects unmethylated lysine 4 of histone H3 to de novo methylation of DNA. Nature 448, 714-717.
106. Otani, J., Nankumo, T., Arita, K., Inamoto, S., Ariyoshi, M., and Shirakawa, M., (2009), Structural basis for recognition of H3K4 methylation status by the DNA methyltransferase 3A ATRX DNMT3-DNMT3L domain. EMBO Rep. 10, 1235-1241. doi: 10.1038/embor.2009.218.
107. Papp, B., and Plath, K., (2013), Epigenetics of reprogramming to induced pluripotency. Cell 152, 1324-1343. doi:10.1016/j.cell.2013.02.043.
108. Pedroso, J.L., Povoas Barsottini, O.G., Lin, L., Melberg, A., Oliveira, A.S., and Mignot, E., (2013), A novel de novo exon 21 DNMT1 mutation causes cerebellar ataxia, deafness, and narcolepsy a Brazilian patient. Sleep 36, 12571259.
109. Peyron, C., Faraco, J., Rogers, W., Ripley, B., Overeem, S., Charnay, Y., et al., (2000), A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains. Nat Med. 6, 991-997.
110. Pfeifer, G.P., Tang, M., and Denissenko, M.F., (2000), Mutation hotspots and DNA methylation. Curr Top Microbiol Immunol. 249, 1-19.
111. Pirola, C.J., Gianotti, T.F., Burgueño, A.L., Rey-Funes, M., Loidl, C.F., Mallardi, P., et al., (2013), Epigenetic modification of liver mitochondrial DNA is associated with histological severity of nonalcoholic fatty liver disease. Gut 62, 1356-1363. doi:10.1136/gutjnl-2012-302962.
112. Pollack, Y., Kasir, J., Shemer, R., Metzger, S., and Szyf, M., (1984), Methylation pattern of mouse mitochondrial DNA. Nucleic Acids Res. 12, 4811-4824.
113. Pradhan, M., Estève, P.O., Chin, H.G., Samaranayke, M., Kim, G.D., and Pradhan, S., (2008), CXXC domain of human DNMT1 is essential for enzymatic activity. Biochemistry 47, 10000- 100009. doi:10.1021/bi8011725.
114. Qin, W., Leonhardt, H., and Pichler, G., (2011), Regulation of DNA methyltransferase 1 by interactions and modifications. Nucleus 2, 392-402. doi:http://dx.doi.org/10.4161/nucl.2.5.17928.
115. Qiu, C., Sawada, K., Zhang, X., and Cheng, X., (2002), The PWWP domain of mammalian DNA methyltransferase Dnmt3b defines a new family of DNA-binding folds. Nat Struct Biol. 9, 217-24.
116. Qureshi, I.A., and Mehler, M.F., (2013), Epigenetic mechanisms governing the process of neurodegeneration. Molecular Aspects of Medicine 34, 875-882.
117. Rao, J.S., Keleshian, V.L., Klein, S., and Rapoport, S.I., (2012), Epigenetic modifications in frontal cortex from Alzheimer's disease and bipolar disorder patients. Transl. Psychiatry 2:e132. doi:10.1038/tp.2012.55.
118. Rebelo, A.P., Williams, S.L., and Moraes, C.T., (2009), In vivo methylation of mtDNA reveals dynamics of protein-mtDNA interactions. Nucleic Acids Res. 37, 6701-6715. doi:10.1093/nar/gkp727.
119. Reik, W., (2007), Stability and flexibility of epigenetic gene regulation i n mammalian development. Nature 447, 425-432. doi:10.1038/nature05918.
120. Riggs, A.D., (1975), X inactivation, differentiation, and DNA methylation. Cytogenet Cell Genet.14, 9-25.
121. Rivera, C.M., and Ren, B., (2013), Mapping human epigenomes. Cell 155, 39-55. doi:10.1016/j.cell.2013.09.011.
122. Robertson, K.D., Uzvolgyi, .E, Liang, G., Talmadge, C., Sumegi, J., Gonzales, F.A., and Jones, P.A., (1999), The human DNA methyltransferases (DNMTs) 1, 3a and 3b: coordinate mRNA expression in normal tissues and overexpression in tumors. Nucleic Acids Res. 27, 2291-2298.
123. Rountree, M.R., Bachman, K.E., and Baylin, S.B. (2000), DNMT1 binds HDAC2 and a new co repressor, DMAP1, to form a complex at replication foci. Nat Genet. 25, 269-277.
124. Schaefer, M., and Lyko, F., (2010), Solving the Dnmt2 enigma. Chromosoma 119, 35-40. doi:10.1007/s00412-009-0240-6.
125. Schaefer, M., Steringer, J.P., and Lyko, F., (2008), The Drosophila cytosine-5 methyltransferase Dnmt2 is associated with the nuclear matrix and can access DNA during mitosis. PLoS ONE 3, e1414
126. Schon, E.A., and Przedborski, S., (2011), Mitochondria: the next (neurode)generation. Neuron 70, 1033-1053. doi: 10.1016/j.neuron.2011.06.003.
127. Sha, K.Y., (2008), A Mechanistic View of Genomic Imprinting. Annu. Rev. Genom. Human Genet. 9, 197-216. doi:10.1146/annurev.genom.122007.110031.
128. Shmookler Reis, R.J. and Goldstein, S., (1983), Mitochondrial DNA in mortal and immortal human cells. Genome number, integrity, and methylation. J Biol Chem. 258, 9078-9085.
129. Shock, L.S., Thakkar, P.V., Peterson, E.J., Moran, R.G., and Taylor, S.M., (2011), DNA methyltransferase 1, cytosine methylation, and cytosine hydroxymethylation in mammalian mitochondria. Proc Natl Acad Sci U S A. 108, 3630-3635.
130. Song, J., Rechkoblit, O., Bestor, T.H., and Patel, D.J., (2011), Structure of DNMT1-DNA complex reveals a role for autoinhibition in maintenance DNA methylation. Science 331, 1036-1040. doi:10.1126/science.1195380.
131. Straub, T., and Becker, P.B., (2007), Dosage compensation: the beginning and end of generalization. Nat Rev Genet. 8, 47-57.
132. Subramaniam, D., Thombre, R., Dhar, A., and Anant, S., (2014), DNA methyltransferases: a novel target for prevention and therapy. Front Oncol. 4, 80. doi:10.3389/fonc.2014.00080.
133. Sung,H.Y.,Choi,E.N.,AhnJo,S.,Oh,S.,andAhn,J.H., (2011), Amyloid protein mediated differential DNA methylation status regulates gene expression in Alzheimer's disease model cell line. Biochem. Biophys. Res. Commun. 414, 700-705. doi:10.1016/j.bbrc.2011.09.136
134. Sun, Z., Wu, Y., Ordog, T., Baheti, S., Nie, J., Duan, X., et al., (2014), Aberrant signature methylome by DNMT1 hot spot mutation in hereditary sensory and autonomic neuropathy 1E. Epigenetics 9, 1184-1193.
135. Syeda, F., Fagan, R.L., Wean, M., Avvakumov, G.V., Walker, J.R., Xue, S., et al., (2011), The replication focus targeting sequence (RFTS) domain is a DNA-competitive inhibitor of Dnmt1. J Biol Chem. 286, 15344-15351. doi:10.1074/jbc.M110.209882.
136. Tafti, M., Hor, H., Dauvilliers, Y., Lammers, G.J., Overeem, S., Mayer, G., et al., (2014), DQB1 locus alone explains most of the risk and protection in narcolepsy with cataplexy in Europe. Sleep 37, 19-25.
137. Takai, D., and Jones, P.A., (2004), Origins of bidirectional promoters: computational analyses of intergenic distance in the human genome. Mol Biol Evol. 21, 463-467.
138. Takeshita, K., Suetake, I., Yamashita, E., Suga, M., Narita, H., Nakagawa, A., and Tajima, S., (2011), Structural insight into maintenance methylation by mouse DNA methyltransferase 1 (Dnmt1). Proc Natl Acad Sci U S A. 108, 9055-9059.
139. Tatton-Brown, K., Seal, S., Ruark, E., Harmer, J., Ramsay, E., Del Vecchio Duarte, S., et al., (2014), Mutations in the DNA methyltransferase gene DNMT3A cause an overgrowth syndrome with intellectual disability. Nat Genet. 46, 385-388. doi:10.1038/ng.2917. Erratum in: Nat Genet. 2014 Jun, 46(6), 657.
140. Valenti, D., Manente, G.A., Moro, L., Marra, E., and Vacca, R.A., (2011), Deficit of complex I activity in human skin fibroblasts with chromosome 21 trisomy and overproduction of reactive oxygen species by mitochondria: involvement of the cAMP/PKA signalling pathway. Biochem J. 435, 679-688. doi:10.1042/BJ20101908.
141. Vanyushin, B.F., and Kirnos, M.D., (1974), The nucleotide composition and pyrimidine clusters in DNA from beef heart mitochondria. FEBS Lett. 39, 195-199.
142. Vanyushin, B.F., and Kirnos, M.D., (1977), Structure of animal mitochondrial DNA (base composition, pyrimidine clusters, character of methylation). Biochim Biophys Acta 475, 323-336.
143. Vanyushin, B.F., Kiryanov, G.I., Kudryashova, I.B., and Belozersky, A.N., (1971), DNA-methylase in loach embryos (Misgurnus fossilis). FEBS Lett. 15, 313-316.
144. Vilkaitis, G., Suetake, I., Klimasauskas, S., and Tajima, S., (2005), Processive methylation of hemimethylated CpG sites by mouse Dnmt1 DNA methyltransferase. J Biol Chem. 280, 64-72.
145. Wang, L., Liu, Y., Beier, U.H., Han, R., Bhatti, T.R., Akimova, T., and Hancock, W.W., (2013), Foxp3+ T-regulatory cells require DNA methyltransferase 1 expression to prevent development of lethal autoimmunity. Blood 121, 3631-3639.
146. Weemaes, C.M., van Tol, M.J., Wang, J., van Ostaijen-ten Dam, M.M., van Eggermond, M.C., Thijssen, P.E., et al., (2013), Heterogeneous clinical presentation in ICF syndrome: correlation with underlying gene defects. Eur J Hum Genet. 21, 1219-1225. doi:10.1038/ejhg.2013.40.
147. Weissman, J., Naidu, S., and Bjornsson, H.T., (2014), Abnormalities of the DNA methylation mark and its machinery: an emerging cause of neurologic dysfunction. Semin Neurol. 34, 249-257. doi:10.1055/s-0034-1386763.
148. Wijsman, E.M., Daw, E.W., Yu, C.E., Payami, H., Steinbart, E.J., Nochlin, D., et al., (2004), Evidence for a novel late-onset Alzheimer disease locus on chromosome 19p13.2. Am J Hum Genet. 75, 398-409.
149. Winkelmann, J., Lin, L., Schormair, B., Kornum, B.R., Faraco, J., Plazzi, G., et al., (2012), Mutations in DNMT1 cause autosomal dominant cerebellar ataxia, deafness and narcolepsy. Hum Mol Genet. 21, 2205-2210. doi:10.1093/hmg/dds035.
150. Wong, M., Gertz, B., Chestnut, B.A., and Martin, L.J., (2013), Mitochondrial DNMT3A and DNA methylation in skeletal muscle and CNS of transgenic mouse models of ALS. Front Cell Neurosci. 7, 279. doi:10.3389/fncel.2013.00279.
151. Wu, B.K., Mei, S.C., and Brenner, C., (2014), RFTS-deleted DNMT1 enhances tumorigenicity with focal hypermethylation and global hypomethylation. Cell Cycle. 13, 3222-3231. doi:10.4161/15384101.2014.950886.
152. Wu, H., and Zhang, Y., (2014), Reversing DNA methylation: mechanisms, genomics, and biological functions. Cell 156, 45-68. doi:10.1016/j.cell.2013.12.019.
153. Wu, H., Zeng, H., Lam, R., Tempel, W., Amaya, M .F., Xu, C., et al., (2011), Structural and histone binding ability characterizations of human PWWP domains. PLoS ONE 6, e18919. doi:10.1371/journal.pone.0018919.
154. Xu, G.L., Bestor, T.H., Bourc'his, D., Hsieh, C.L., Tommerup, N., Bugge, M., et al., (1999), Chromosome instability and immunodeficiency syndrome caused by mutations in a DNA methyltransferase gene. Nature 402, 187-91.
155. Yu, L., Chibnik, L.B., Srivastava, G.P., Pochet, N., Yang, J., Xu, J., et al., (2014), Association of Brain DNA Methylation in SORL1, ABCA7, HLA-DRB5, SLC24A4, and BIN1 With Pathological Diagnosis of Alzheimer Disease. JAMA Neurol. Nov 3. doi:10.1001/jamaneurol.2014.3049.
156. Yuan, J., Higuchi, Y., Nagado, T., Nozuma, S., Nakamura, T., Matsuura, E., et al., (2013), Novel mutation in the replication focus targeting sequence domain of DNMT1 causes hereditary sensory and autonomic neuropathy IE. J Peripher Nerv Syst. 18, 89-93.
157. Zhang, Y., Jurkowska, R., Soeroes, S., Rajavelu, A., Dhayalan, A., Bock, I., et al., (2010), Chromatin methylation activity of Dnmt3a and Dnmt3a/3L is guided by interaction of the ADD domain with the histone H3 tail. Nucleic Acids Res. 38, 4246-53. doi:10.1093/nar/gkq147.