12. Maiti A, Drohat AC (2011) Thymine DNA glycosylase can rapidly excise 5-formylcytosine
and 5-carboxylcytosine. J Biol Chem 286:35334–35338. https://doi.org/10.1074/jbc.C111.
284620
13. Iwan K, Rahimoff R, Kirchner A et al (2018) 5-formylcytosine to cytosine conversion by C-C
bond cleavage in vivo. Nat Chem Biol 14:72–78. https://doi.org/10.1038/nchembio.2531
14. Zhu J-K (2009) Active DNA demethylation mediated by DNA glycosylases. Annu Rev Genet
43:143–166. https://doi.org/10.1146/annurev-genet-102108-134205
15. Holliday R, Pugh JE (1975) DNA modification mechanisms and gene activity during development. Science 187:226–232
16. Riggs AD (1975) X inactivation, differentiation, and DNA methylation. Cytogenet Genome
Res 14:9–25. https://doi.org/10.1159/000130315
17. Drahovsky D, Boehm TLJ (1980) Enzymatic dna methylation in higher eukaryotes. Int J
Biochem 12:523–528. https://doi.org/10.1016/0020-711X(80)90002-6
18. Bestor T, Laudano A, Mattaliano R, Ingram V (1988) Cloning and sequencing of a cDNA
encoding DNA methyltransferase of mouse cells: the carboxyl-terminal domain of the mammalian enzymes is related to bacterial restriction methyltransferases. J Mol Biol 203:971–983.
https://doi.org/10.1016/0022-2836(88)90122-2
19. Okano M, Xie S, Li E (1998) Cloning and characterization of a family of novel mammalian
DNA (cytosine-5) methyltransferases. Nat Genet 19:219–220. https://doi.org/10.1038/890
20. Aapola U, Shibuya K, Scott HS et al (2000) Isolation and initial characterization of a novel
zinc finger gene, DNMT3L, on 21q22.3, related to the cytosine-5- methyltransferase 3 gene
family. Genomics 65:293–298. https://doi.org/10.1006/GENO.2000.6168
21. Bourc’his D, Xu GL, Lin CS et al (2001) Dnmt3L and the establishment of maternal genomic
imprints. Science 294:2536–2539. https://doi.org/10.1126/science.1065848
22. Jia D, Jurkowska RZ, Zhang X et al (2007) Structure of Dnmt3a bound to Dnmt3L suggests a
model for de novo DNA methylation. Nature 449:248–251. https://doi.org/10.1038/
nature06146
23. Lyko F (2018) The DNA methyltransferase family: a versatile toolkit for epigenetic regulation.
Nat Rev Genet 19:81–92. https://doi.org/10.1038/nrg.2017.80
24. Rondelet G, Wouters J (2017) Human DNA (cytosine-5)-methyltransferases: a functional and
structural perspective for epigenetic cancer therapy. Biochimie 139:137–147. https://doi.org/
10.1016/J.BIOCHI.2017.06.003
25. Jurkowski TP, Jeltsch A (2011) On the evolutionary origin of eukaryotic DNA
methyltransferases and Dnmt2. PLoS One 6:e28104. https://doi.org/10.1371/journal.pone.
0028104
26. Gowher H, Jeltsch A (2018) Mammalian DNA methyltransferases: new discoveries and open
questions. Biochem Soc Trans 46:1191–1202. https://doi.org/10.1042/BST20170574
27. Qin S, Min J (2014) Structure and function of the nucleosome-binding PWWP domain. Trends
Biochem Sci 39:536–547. https://doi.org/10.1016/j.tibs.2014.09.001
28. Yarychkivska O, Shahabuddin Z, Comfort N et al (2018) BAH domains and a histone-like
motif in DNA methyltransferase 1 (DNMT1) regulate de novo and maintenance methylation
in vivo. J Biol Chem 293:19466–19475. https://doi.org/10.1074/jbc.RA118.004612
29. Zhang ZM, Liu S, Lin K et al (2015) Crystal structure of human DNA methyltransferase
1. J Mol Biol 427:2520–2531. https://doi.org/10.1016/j.jmb.2015.06.001
30. Ye F, Kong X, Zhang H et al (2018) Biochemical studies and molecular dynamic simulations
reveal the molecular basis of conformational changes in DNA methyltransferase-1. ACS Chem
Biol 13:772–781. https://doi.org/10.1021/acschembio.7b00890
31. Issa J-PJ, Kantarjian HM (2009) Targeting DNA methylation. Clin Cancer Res 15:3938–3946.
https://doi.org/10.1158/1078-0432.CCR-08-2783
32. Jones PA, Baylin SB (2007) The epigenomics of cancer. Cell 128:683–692. https://doi.org/10.
1016/j.cell.2007.01.029
33. Baylin SB, Jones PA (2016) Epigenetic determinants of cancer. Cold Spring Harb Perspect
Biol 8:a019505. https://doi.org/10.1101/cshperspect.a019505
34. Feinberg AP, Ohlsson R, Henikoff S (2006) The epigenetic progenitor origin of human cancer.
Nat Rev Genet 7:21–33
Chemical Compounds Targeting DNA Methylation and Hydroxymethylation
279
and 5-carboxylcytosine. J Biol Chem 286:35334–35338. https://doi.org/10.1074/jbc.C111.
284620
13. Iwan K, Rahimoff R, Kirchner A et al (2018) 5-formylcytosine to cytosine conversion by C-C
bond cleavage in vivo. Nat Chem Biol 14:72–78. https://doi.org/10.1038/nchembio.2531
14. Zhu J-K (2009) Active DNA demethylation mediated by DNA glycosylases. Annu Rev Genet
43:143–166. https://doi.org/10.1146/annurev-genet-102108-134205
15. Holliday R, Pugh JE (1975) DNA modification mechanisms and gene activity during development. Science 187:226–232
16. Riggs AD (1975) X inactivation, differentiation, and DNA methylation. Cytogenet Genome
Res 14:9–25. https://doi.org/10.1159/000130315
17. Drahovsky D, Boehm TLJ (1980) Enzymatic dna methylation in higher eukaryotes. Int J
Biochem 12:523–528. https://doi.org/10.1016/0020-711X(80)90002-6
18. Bestor T, Laudano A, Mattaliano R, Ingram V (1988) Cloning and sequencing of a cDNA
encoding DNA methyltransferase of mouse cells: the carboxyl-terminal domain of the mammalian enzymes is related to bacterial restriction methyltransferases. J Mol Biol 203:971–983.
https://doi.org/10.1016/0022-2836(88)90122-2
19. Okano M, Xie S, Li E (1998) Cloning and characterization of a family of novel mammalian
DNA (cytosine-5) methyltransferases. Nat Genet 19:219–220. https://doi.org/10.1038/890
20. Aapola U, Shibuya K, Scott HS et al (2000) Isolation and initial characterization of a novel
zinc finger gene, DNMT3L, on 21q22.3, related to the cytosine-5- methyltransferase 3 gene
family. Genomics 65:293–298. https://doi.org/10.1006/GENO.2000.6168
21. Bourc’his D, Xu GL, Lin CS et al (2001) Dnmt3L and the establishment of maternal genomic
imprints. Science 294:2536–2539. https://doi.org/10.1126/science.1065848
22. Jia D, Jurkowska RZ, Zhang X et al (2007) Structure of Dnmt3a bound to Dnmt3L suggests a
model for de novo DNA methylation. Nature 449:248–251. https://doi.org/10.1038/
nature06146
23. Lyko F (2018) The DNA methyltransferase family: a versatile toolkit for epigenetic regulation.
Nat Rev Genet 19:81–92. https://doi.org/10.1038/nrg.2017.80
24. Rondelet G, Wouters J (2017) Human DNA (cytosine-5)-methyltransferases: a functional and
structural perspective for epigenetic cancer therapy. Biochimie 139:137–147. https://doi.org/
10.1016/J.BIOCHI.2017.06.003
25. Jurkowski TP, Jeltsch A (2011) On the evolutionary origin of eukaryotic DNA
methyltransferases and Dnmt2. PLoS One 6:e28104. https://doi.org/10.1371/journal.pone.
0028104
26. Gowher H, Jeltsch A (2018) Mammalian DNA methyltransferases: new discoveries and open
questions. Biochem Soc Trans 46:1191–1202. https://doi.org/10.1042/BST20170574
27. Qin S, Min J (2014) Structure and function of the nucleosome-binding PWWP domain. Trends
Biochem Sci 39:536–547. https://doi.org/10.1016/j.tibs.2014.09.001
28. Yarychkivska O, Shahabuddin Z, Comfort N et al (2018) BAH domains and a histone-like
motif in DNA methyltransferase 1 (DNMT1) regulate de novo and maintenance methylation
in vivo. J Biol Chem 293:19466–19475. https://doi.org/10.1074/jbc.RA118.004612
29. Zhang ZM, Liu S, Lin K et al (2015) Crystal structure of human DNA methyltransferase
1. J Mol Biol 427:2520–2531. https://doi.org/10.1016/j.jmb.2015.06.001
30. Ye F, Kong X, Zhang H et al (2018) Biochemical studies and molecular dynamic simulations
reveal the molecular basis of conformational changes in DNA methyltransferase-1. ACS Chem
Biol 13:772–781. https://doi.org/10.1021/acschembio.7b00890
31. Issa J-PJ, Kantarjian HM (2009) Targeting DNA methylation. Clin Cancer Res 15:3938–3946.
https://doi.org/10.1158/1078-0432.CCR-08-2783
32. Jones PA, Baylin SB (2007) The epigenomics of cancer. Cell 128:683–692. https://doi.org/10.
1016/j.cell.2007.01.029
33. Baylin SB, Jones PA (2016) Epigenetic determinants of cancer. Cold Spring Harb Perspect
Biol 8:a019505. https://doi.org/10.1101/cshperspect.a019505
34. Feinberg AP, Ohlsson R, Henikoff S (2006) The epigenetic progenitor origin of human cancer.
Nat Rev Genet 7:21–33
Chemical Compounds Targeting DNA Methylation and Hydroxymethylation
279