133. Takai H, Masuda K, Sato T et al (2014) 5-Hydroxymethylcytosine plays a critical role in
glioblastomagenesis by recruiting the CHTOP-methylosome complex. Cell Rep 9:48–60.
https://doi.org/10.1016/j.celrep.2014.08.071
134. Rasmussen KD, Helin K (2016) Role of TET enzymes in DNA methylation, development, and
cancer. Genes Dev 30:733–750. https://doi.org/10.1101/gad.276568.115
135. Langemeijer SMC, Kuiper RP, Berends M et al (2009) Acquired mutations in TET2 are common
in myelodysplastic syndromes. Nat Genet 41:838–842. https://doi.org/10.1038/ng.391
136. Weissmann S, Alpermann T, Grossmann V et al (2012) Landscape of TET2 mutations in acute
myeloid leukemia. Leukemia 26:934–942. https://doi.org/10.1038/leu.2011.326
137. Quivoron C, Couronné L, Della Valle V et al (2011) TET2 inactivation results in pleiotropic
hematopoietic abnormalities in mouse and is a recurrent event during human lymphomagenesis.
Cancer Cell 20:25–38. https://doi.org/10.1016/J.CCR.2011.06.003
138. Quesada V, Conde L, Villamor N et al (2012) Exome sequencing identifies recurrent mutations of the splicing factor SF3B1 gene in chronic lymphocytic leukemia. Nat Genet 44:47–52.
https://doi.org/10.1038/ng.1032
139. Yang H, Liu Y, Bai F et al (2013) Tumor development is associated with decrease of TET gene
expression and 5-methylcytosine hydroxylation. Oncogene 32:663–669. https://doi.org/10.
1038/onc.2012.67
140. Bachman M, Uribe-Lewis S, Yang X et al (2014) 5-Hydroxymethylcytosine is a predominantly stable DNA modification. Nat Chem 6:1049–1055. https://doi.org/10.1038/nchem.
2064
141. Song C-X, Yi C, He C (2012) Mapping recently identified nucleotide variants in the genome
and transcriptome. Nat Biotechnol 30:1107–1116. https://doi.org/10.1038/nbt.2398
142. Terragni J, Bitinaite J, Zheng Y, Pradhan S (2012) Biochemical characterization of recombinant β-glucosyltransferase and analysis of global 5-hydroxymethylcytosine in unique
genomes. Biochemistry 51:1009–1019. https://doi.org/10.1021/bi2014739
143. Booth MJ, Raiber E-A, Balasubramanian S (2015) Chemical methods for decoding cytosine
modifications in DNA. Chem Rev 115:2240–2254. https://doi.org/10.1021/cr5002904
144. Tahiliani M, Koh KP, Shen Y et al (2015) Conversion 5-hydroxymethylcytosine in Mammalian DNA by MuL partner TETi. Science 324:930–936
145. Münzel M, Globisch D, Brückl T et al (2010) Quantification of the sixth DNA base
hydroxymethylcytosine in the brain. Angew Chem Int Ed 49:5375–5377. https://doi.org/10.
1002/anie.201002033
146. Kinney SM, Chin HG, Vaisvila R et al (2011) Tissue-specific distribution and dynamic changes
of 5-hydroxymethylcytosine in mammalian genomes. J Biol Chem 286:24685–24693. https://
doi.org/10.1074/jbc.M110.217083
147. Szwagierczak A, Bultmann S, Schmidt CS et al (2010) Sensitive enzymatic quantification of
5-hydroxymethylcytosine in genomic DNA. Nucleic Acids Res 38:e181–e181. https://doi.org/
10.1093/nar/gkq684
148. Booth MJ, Branco MR, Ficz G et al (2012) Quantitative sequencing of 5-methylcytosine and
5-hydroxymethylcytosine at single-base resolution. Science 336:934–937. https://doi.org/10.
1126/science.1220671
149. Pastor WA, Pape UJ, Huang Y et al (2011) Genome-wide mapping of
5-hydroxymethylcytosine in embryonic stem cells. Nature 473:394–397. https://doi.org/10.
1038/nature10102
150. Song CX, Szulwach KE, Fu Y et al (2011) Selective chemical labeling reveals the genomewide distribution of 5-hydroxymethylcytosine. Nat Biotechnol 29:68–75. https://doi.org/10.
1038/nbt.1732
151. Yu M, Hon GC, Szulwach KE et al (2012) Tet-assisted bisulfite sequencing of
5-hydroxymethylcytosine. Nat Protoc 7:2159–2170. https://doi.org/10.1038/nprot.2012.137
152. Flusberg BA, Webster DR, Lee JH et al (2010) Direct detection of DNA methylation during
single-molecule, real-time sequencing. Nat Methods 7:461–465. https://doi.org/10.1038/
nmeth.1459
Chemical Compounds Targeting DNA Methylation and Hydroxymethylation
285
glioblastomagenesis by recruiting the CHTOP-methylosome complex. Cell Rep 9:48–60.
https://doi.org/10.1016/j.celrep.2014.08.071
134. Rasmussen KD, Helin K (2016) Role of TET enzymes in DNA methylation, development, and
cancer. Genes Dev 30:733–750. https://doi.org/10.1101/gad.276568.115
135. Langemeijer SMC, Kuiper RP, Berends M et al (2009) Acquired mutations in TET2 are common
in myelodysplastic syndromes. Nat Genet 41:838–842. https://doi.org/10.1038/ng.391
136. Weissmann S, Alpermann T, Grossmann V et al (2012) Landscape of TET2 mutations in acute
myeloid leukemia. Leukemia 26:934–942. https://doi.org/10.1038/leu.2011.326
137. Quivoron C, Couronné L, Della Valle V et al (2011) TET2 inactivation results in pleiotropic
hematopoietic abnormalities in mouse and is a recurrent event during human lymphomagenesis.
Cancer Cell 20:25–38. https://doi.org/10.1016/J.CCR.2011.06.003
138. Quesada V, Conde L, Villamor N et al (2012) Exome sequencing identifies recurrent mutations of the splicing factor SF3B1 gene in chronic lymphocytic leukemia. Nat Genet 44:47–52.
https://doi.org/10.1038/ng.1032
139. Yang H, Liu Y, Bai F et al (2013) Tumor development is associated with decrease of TET gene
expression and 5-methylcytosine hydroxylation. Oncogene 32:663–669. https://doi.org/10.
1038/onc.2012.67
140. Bachman M, Uribe-Lewis S, Yang X et al (2014) 5-Hydroxymethylcytosine is a predominantly stable DNA modification. Nat Chem 6:1049–1055. https://doi.org/10.1038/nchem.
2064
141. Song C-X, Yi C, He C (2012) Mapping recently identified nucleotide variants in the genome
and transcriptome. Nat Biotechnol 30:1107–1116. https://doi.org/10.1038/nbt.2398
142. Terragni J, Bitinaite J, Zheng Y, Pradhan S (2012) Biochemical characterization of recombinant β-glucosyltransferase and analysis of global 5-hydroxymethylcytosine in unique
genomes. Biochemistry 51:1009–1019. https://doi.org/10.1021/bi2014739
143. Booth MJ, Raiber E-A, Balasubramanian S (2015) Chemical methods for decoding cytosine
modifications in DNA. Chem Rev 115:2240–2254. https://doi.org/10.1021/cr5002904
144. Tahiliani M, Koh KP, Shen Y et al (2015) Conversion 5-hydroxymethylcytosine in Mammalian DNA by MuL partner TETi. Science 324:930–936
145. Münzel M, Globisch D, Brückl T et al (2010) Quantification of the sixth DNA base
hydroxymethylcytosine in the brain. Angew Chem Int Ed 49:5375–5377. https://doi.org/10.
1002/anie.201002033
146. Kinney SM, Chin HG, Vaisvila R et al (2011) Tissue-specific distribution and dynamic changes
of 5-hydroxymethylcytosine in mammalian genomes. J Biol Chem 286:24685–24693. https://
doi.org/10.1074/jbc.M110.217083
147. Szwagierczak A, Bultmann S, Schmidt CS et al (2010) Sensitive enzymatic quantification of
5-hydroxymethylcytosine in genomic DNA. Nucleic Acids Res 38:e181–e181. https://doi.org/
10.1093/nar/gkq684
148. Booth MJ, Branco MR, Ficz G et al (2012) Quantitative sequencing of 5-methylcytosine and
5-hydroxymethylcytosine at single-base resolution. Science 336:934–937. https://doi.org/10.
1126/science.1220671
149. Pastor WA, Pape UJ, Huang Y et al (2011) Genome-wide mapping of
5-hydroxymethylcytosine in embryonic stem cells. Nature 473:394–397. https://doi.org/10.
1038/nature10102
150. Song CX, Szulwach KE, Fu Y et al (2011) Selective chemical labeling reveals the genomewide distribution of 5-hydroxymethylcytosine. Nat Biotechnol 29:68–75. https://doi.org/10.
1038/nbt.1732
151. Yu M, Hon GC, Szulwach KE et al (2012) Tet-assisted bisulfite sequencing of
5-hydroxymethylcytosine. Nat Protoc 7:2159–2170. https://doi.org/10.1038/nprot.2012.137
152. Flusberg BA, Webster DR, Lee JH et al (2010) Direct detection of DNA methylation during
single-molecule, real-time sequencing. Nat Methods 7:461–465. https://doi.org/10.1038/
nmeth.1459
Chemical Compounds Targeting DNA Methylation and Hydroxymethylation
285