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beyond. Genes (Basel) 5:821–864. https://doi.org/10.3390/genes5030821
37. Leygo C, Williams M, Jin HC et al (2017) DNA methylation as a noninvasive epigenetic
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38. Ahuja N, Sharma AR, Baylin SB (2016) Epigenetic therapeutics: a new weapon in the war
against cancer. Annu Rev Med 67:73–89. https://doi.org/10.1146/annurev-med-111314035900
39. Ahuja N, Easwaran H, Baylin SB (2014) Harnessing the potential of epigenetic therapy to
target solid tumors. J Clin Invest 124:56–63. https://doi.org/10.1172/JCI69736
40. Feinberg AP (2007) Phenotypic plasticity and the epigenetics of human disease. Nature
447:433–440. https://doi.org/10.1038/nature05919
41. Velasco G, Francastel C (2018) Genetics meets DNA methylation in rare diseases. Clin Genet
95:210–220. https://doi.org/10.1111/cge.13480
42. Lopez M, Halby L, Arimondo PB (2016) DNA methyltransferase inhibitors: development and
applications. Adv Exp Med Biol 945:431–473. https://doi.org/10.1007/978-3-319-43624-1_16
43. Andersen GB, Tost J (2018) A summary of the biological processes, disease-associated
changes, and clinical applications of DNA methylation. Methods Mol Biol 1708:3–30
44. Jones PA, Issa J-PJ, Baylin S (2016) Targeting the cancer epigenome for therapy. Nat Rev
Genet 17:630–641. https://doi.org/10.1038/nrg.2016.93
45. Okano M, Xie S, Li E (1998) Dnmt2 is not required for de novo and maintenance methylation
of viral DNA in embryonic stem cells. Nucleic Acids Res 26:2536–2540
46. Tuorto F, Liebers R, Musch T et al (2012) RNA cytosine methylation by Dnmt2 and NSun2
promotes tRNA stability and protein synthesis. Nat Struct Mol Biol 19:900–905. https://doi.
org/10.1038/nsmb.2357
47. Goll MG, Kirpekar F, Maggert KA et al (2006) Methylation of tRNAAsp by the DNA
methyltransferase homolog Dnmt2. Science 311:395–398. https://doi.org/10.1126/science.
1120976
48. Govindaraju G, Jabeena C, Sethumadhavan DV et al (2017) DNA methyltransferase homologue TRDMT1 in plasmodium falciparum specifically methylates endogenous aspartic acid
tRNA. Biochim Biophys Acta-Gene Regul Mech 1860:1047–1057. https://doi.org/10.1016/j.
bbagrm.2017.08.003
49. Capuano F, Mülleder M, Kok R et al (2014) Cytosine DNA methylation is found in Drosophila melanogaster but absent in Saccharomyces cerevisiae, Schizosaccharomyces pombe,
and other yeast species. Anal Chem 86:3697–3702. https://doi.org/10.1021/ac500447w
50. Zadražil S, Fučík V, Bartl P et al (1965) The structure of DNA from Escherichia coli cultured
in the presence of 5-azacytidine. Biochim Biophys Acta Nucleic Acids Protein Synth
108:701–703. https://doi.org/10.1016/0005-2787(65)90066-3
51. Sorm F, Vesely J (1964) The activity of a new antimetabolite, 5-azacytidine, against lymphoid.
Neoplasma 11:123–130
52. Taylor SM, Jones PA (1979) Multiple new phenotypes induced in 10T1/2 and 3T3 cells
treated with 5-azacytidine. Cell 17:771–779
53. Jones PA, Taylor SM (1980) Cellular differentiation, cytidine analogs and DNA methylation.
Cell 20:85–93
54. Santi DV, Garrett CE, Barr PJ (1983) On the mechanism of inhibition of DNA-cytosine
methyltransferases by cytosine analogs. Cell 33:9–10. https://doi.org/10.1016/0092-8674(83)
90327-6
55. Santi DV, Norment A, Garrett CE (1984) Covalent bond formation between a DNA-cytosine
methyltransferase and DNA containing 5-azacytosine. Proc Natl Acad Sci U S A
81:6993–6997
280
R. Belle et al.
N Engl J Med 378:1323–1334. https://doi.org/10.1056/NEJMra1402513
36. Mikeska T, Craig J, Mikeska T, Craig JM (2014) DNA methylation biomarkers: cancer and
beyond. Genes (Basel) 5:821–864. https://doi.org/10.3390/genes5030821
37. Leygo C, Williams M, Jin HC et al (2017) DNA methylation as a noninvasive epigenetic
biomarker for the detection of cancer. Dis Markers 2017:1–13. https://doi.org/10.1155/2017/
3726595
38. Ahuja N, Sharma AR, Baylin SB (2016) Epigenetic therapeutics: a new weapon in the war
against cancer. Annu Rev Med 67:73–89. https://doi.org/10.1146/annurev-med-111314035900
39. Ahuja N, Easwaran H, Baylin SB (2014) Harnessing the potential of epigenetic therapy to
target solid tumors. J Clin Invest 124:56–63. https://doi.org/10.1172/JCI69736
40. Feinberg AP (2007) Phenotypic plasticity and the epigenetics of human disease. Nature
447:433–440. https://doi.org/10.1038/nature05919
41. Velasco G, Francastel C (2018) Genetics meets DNA methylation in rare diseases. Clin Genet
95:210–220. https://doi.org/10.1111/cge.13480
42. Lopez M, Halby L, Arimondo PB (2016) DNA methyltransferase inhibitors: development and
applications. Adv Exp Med Biol 945:431–473. https://doi.org/10.1007/978-3-319-43624-1_16
43. Andersen GB, Tost J (2018) A summary of the biological processes, disease-associated
changes, and clinical applications of DNA methylation. Methods Mol Biol 1708:3–30
44. Jones PA, Issa J-PJ, Baylin S (2016) Targeting the cancer epigenome for therapy. Nat Rev
Genet 17:630–641. https://doi.org/10.1038/nrg.2016.93
45. Okano M, Xie S, Li E (1998) Dnmt2 is not required for de novo and maintenance methylation
of viral DNA in embryonic stem cells. Nucleic Acids Res 26:2536–2540
46. Tuorto F, Liebers R, Musch T et al (2012) RNA cytosine methylation by Dnmt2 and NSun2
promotes tRNA stability and protein synthesis. Nat Struct Mol Biol 19:900–905. https://doi.
org/10.1038/nsmb.2357
47. Goll MG, Kirpekar F, Maggert KA et al (2006) Methylation of tRNAAsp by the DNA
methyltransferase homolog Dnmt2. Science 311:395–398. https://doi.org/10.1126/science.
1120976
48. Govindaraju G, Jabeena C, Sethumadhavan DV et al (2017) DNA methyltransferase homologue TRDMT1 in plasmodium falciparum specifically methylates endogenous aspartic acid
tRNA. Biochim Biophys Acta-Gene Regul Mech 1860:1047–1057. https://doi.org/10.1016/j.
bbagrm.2017.08.003
49. Capuano F, Mülleder M, Kok R et al (2014) Cytosine DNA methylation is found in Drosophila melanogaster but absent in Saccharomyces cerevisiae, Schizosaccharomyces pombe,
and other yeast species. Anal Chem 86:3697–3702. https://doi.org/10.1021/ac500447w
50. Zadražil S, Fučík V, Bartl P et al (1965) The structure of DNA from Escherichia coli cultured
in the presence of 5-azacytidine. Biochim Biophys Acta Nucleic Acids Protein Synth
108:701–703. https://doi.org/10.1016/0005-2787(65)90066-3
51. Sorm F, Vesely J (1964) The activity of a new antimetabolite, 5-azacytidine, against lymphoid.
Neoplasma 11:123–130
52. Taylor SM, Jones PA (1979) Multiple new phenotypes induced in 10T1/2 and 3T3 cells
treated with 5-azacytidine. Cell 17:771–779
53. Jones PA, Taylor SM (1980) Cellular differentiation, cytidine analogs and DNA methylation.
Cell 20:85–93
54. Santi DV, Garrett CE, Barr PJ (1983) On the mechanism of inhibition of DNA-cytosine
methyltransferases by cytosine analogs. Cell 33:9–10. https://doi.org/10.1016/0092-8674(83)
90327-6
55. Santi DV, Norment A, Garrett CE (1984) Covalent bond formation between a DNA-cytosine
methyltransferase and DNA containing 5-azacytosine. Proc Natl Acad Sci U S A
81:6993–6997
280
R. Belle et al.