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binding by 2-oxoglutarate oxygenases. Curr Opin Struct Biol 22:691–700. https://doi.org/10.
1016/j.sbi.2012.10.001
114. Hu L, Li Z, Cheng J et al (2013) Crystal structure of TET2-DNA complex: insight into
TET-mediated 5mC oxidation. Cell 155:1545–1555. https://doi.org/10.1016/j.cell.2013.11.020
115. Shen L, Song C-X, He C, Zhang Y (2014) Mechanism and function of oxidative reversal of
DNA and RNA methylation. Annu Rev Biochem 83:585–614. https://doi.org/10.1146/
annurev-biochem-060713-035513
116. McDonough MA, Loenarz C, Chowdhury R et al (2010) Structural studies on human
2-oxoglutarate dependent oxygenases. Curr Opin Struct Biol 20:659–672. https://doi.org/10.
1016/j.sbi.2010.08.006
117. Loenarz C, Schofield CJ (2008) Expanding chemical biology of 2-oxoglutarate oxygenases.
Nat Chem Biol 4:152–156. https://doi.org/10.1038/nchembio0308-152
118. Hu L, Lu J, Cheng J et al (2015) Structural insight into substrate preference for TET-mediated
oxidation. Nature 527:118–122. https://doi.org/10.1038/nature15713
119. Fu L, Guerrero CR, Zhong N et al (2014) Tet-mediated formation of 5-hydroxymethylcytosine
in RNA. J Am Chem Soc 136:11582–11585. https://doi.org/10.1021/ja505305z
120. Schröder AS, Parsa E, Iwan K et al (2016) 2
0 -(R)-fluorinated mC, hmC, fC and caC triphosphates are substrates for DNA polymerases and TET-enzymes. Chem Commun
52:14361–14364. https://doi.org/10.1039/C6CC07517G
121. Pais JE, Dai N, Tamanaha E et al (2015) Biochemical characterization of a Naegleria TET-like
oxygenase and its application in single molecule sequencing of 5-methylcytosine. Proc Natl
Acad Sci 112:4316–4321. https://doi.org/10.1073/pnas.1417939112
122. Pfaffeneder T, Spada F, Wagner M et al (2014) Tet oxidizes thymine to 5-hydroxymethyluracil
in mouse embryonic stem cell DNA. Nat Chem Biol 10:574–581. https://doi.org/10.1038/
nchembio.1532
123. Deaton AM, Bird A (2011) CpG islands and the regulation of transcription. Genes Dev
25:1010–1022. https://doi.org/10.1101/gad.2037511
124. Globisch D, Münzel M, Müller M et al (2010) Tissue distribution of 5-hydroxymethylcytosine
and search for active demethylation intermediates. PLoS One 5:e15367. https://doi.org/10.
1371/journal.pone.0015367
125. Bachman M, Uribe-Lewis S, Yang X et al (2015) 5-formylcytosine can be a stable DNA
modification in mammals. Nat Chem Biol 11:555–557. https://doi.org/10.1038/nchembio.
1848
126. Xu Y, Wu F, Tan L et al (2011) Genome-wide regulation of 5hmC, 5mC, and gene expression
by Tet1 hydroxylase in mouse embryonic stem cells. Mol Cell 42:451–464. https://doi.org/10.
1016/J.MOLCEL.2011.04.005
127. Raiber E-A, Murat P, Chirgadze DY et al (2015) 5-Formylcytosine alters the structure of the
DNA double helix. Nat Struct Mol Biol 22:44–49. https://doi.org/10.1038/nsmb.2936
128. Hardwick JS, Ptchelkine D, El-Sagheer AH et al (2017) 5-Formylcytosine does not change the
global structure of DNA. Nat Struct Mol Biol 24:544–552. https://doi.org/10.1038/nsmb.3411
129. Raiber E-A, Portella G, Cuesta SM et al (2017) 5-Formylcytosine controls nucleosome
positioning through covalent histone-DNA interaction. bioRxiv:224444. https://doi.org/10.
1101/224444
130. Kellinger MW, Song C-X, Chong J et al (2012) 5-Formylcytosine and 5-carboxylcytosine
reduce the rate and substrate specificity of RNA polymerase II transcription. Nat Struct Mol
Biol 19:831–833. https://doi.org/10.1038/nsmb.2346
131. Iurlaro M, Ficz G, Oxley D et al (2013) A screen for hydroxymethylcytosine and
formylcytosine binding proteins suggests functions in transcription and chromatin regulation.
Genome Biol 14:R119. https://doi.org/10.1186/gb-2013-14-10-r119
132. Huang H, Jiang X, Li Z et al (2013) TET1 plays an essential oncogenic role in
MLL-rearranged leukemia. Proc Natl Acad Sci 110:11994–11999. https://doi.org/10.1073/
pnas.1310656110
284
R. Belle et al.