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82. Yu-Fei H, Bin-Zhong L, Zheng L, Peng L, Yang W, Qingyu T, Jianping D, Yingying J,
Zhangcheng C, Lin L, Yan S, Xiuxue L, Qing D, Chun-Xiao S, Kangling Z, Chuan H,
Guo-Liang X (2011) Tet-mediated formation of 5-carboxylcytosine and its excision by TDG
in mammalian DNA. Science 333:1303–1307. https://doi.org/10.1126/science.1229223
83. Zhang L, Lu X, Lu J, Liang H, Dai Q, Xu GL, Luo C, Jiang H, He C (2012) Thymine DNA
glycosylase specifically recognizes 5-carboxylcytosine-modified DNA. Nat Chem Biol
8:328–330. https://doi.org/10.1038/nchembio.914
84. Slupphaug G, Mol CD, Kavli B, Arvai AS, Krokan HE, Tainer JA (1996) A nucleotideflipping mechanism from the structure of human uracil–DNA glycosylase bound to DNA.
Nature 384:87
85. Kooistra SM, Helin K (2012) Molecular mechanisms and potential functions of histone
demethylases. Nat Rev Mol Cell Biol 13:297–311. https://doi.org/10.1038/nrm3327
450
M. R. H. Zwinderman et al.
Histone deacetylase HDAC8 associates with smooth muscle alpha-actin and is essential for
smooth muscle cell contractility. FASEB J 19:966–968. https://doi.org/10.1096/fj.04-2303fje
70. Li J, Chen S, Cleary RA, Wang R, Gannon OJ, Seto E, Tang DD (2014) Histone deacetylase
8 regulates cortactin deacetylation and contraction in smooth muscle tissues. Am J Physiol
Cell Physiol 307:C288–C295. https://doi.org/10.1152/ajpcell.00102.2014
71. Balasubramanian S, Ramos J, Luo W, Sirisawad M, Verner E, Buggy JJ (2008) A novel
histone deacetylase 8 (HDAC8)-specific inhibitor PCI-34051 induces apoptosis in T-cell
lymphomas. Leukemia 22:1026–1034. https://doi.org/10.1038/leu.2008.9
72. Ren Y, Su X, Kong L, Li M, Zhao X, Yu N, Kang J (2016) Therapeutic effects of histone
deacetylase inhibitors in a murine asthma model. Inflamm Res 65:995–1008. https://doi.org/
10.1007/s00011-016-0984-4
73. Hubbert C, Guardiola A, Shao R, Kawaguchi Y, Ito A, Nixon A, Yoshida M, Wang XF, Yao
TP (2002) HDAC6 is a microtubule-associated deacetylase. Nature 417:455–458. https://doi.
org/10.1038/417455a
74. Zhang Y, Li N, Caron C, Matthias G, Hess D, Khochbin S, Matthias P (2003) HDAC-6
interacts with and deacetylates tubulin and microtubules in vivo. EMBO J 22:1168–1179.
https://doi.org/10.1093/emboj/cdg115
75. Razin A, Cedar H (1991) DNA methylation and gene expression. Microbiol Rev 55:451–458
76. Stresemann C, Lyko F (2008) Modes of action of the DNA methyltransferase inhibitors
azacytidine and decitabine. Int J Cancer 123:8–13. https://doi.org/10.1002/ijc.23607
77. Tsai HC, Li H, Van Neste L, Cai Y, Robert C, Rassool FV, Shin JJ, Harbom KM, Beaty R,
Pappou E, Harris J, Yen RWC, Ahuja N, Brock MV, Stearns V, Feller-Kopman D, Yarmus
LB, Lin YC, Welm AL, Issa JP, Minn I, Matsui W, Jang YY, Sharkis SJ, Baylin SB, Zahnow
CA (2012) Transient low doses of DNA-demethylating agents exert durable antitumor effects
on hematological and epithelial tumor cells. Cancer Cell 21:430–446. https://doi.org/10.1016/
j.ccr.2011.12.029
78. Tahiliani M, Koh KP, Shen Y, Pastor WA, Bandukwala H, Brudno Y, Agarwal S, Iyer LM, Liu
DR, Aravind L, Rao A (2009) Conversion of 5-Methylcytosine to 5-Hydroxymethylcytosine in
mammalian DNA by MLL partner TET1. Science 324:930–935. https://doi.org/10.1126/sci
ence.1170116
79. Ito S, Shen L, Dai Q, Wu SC, Collins LB, Swenberg JA, He C, Zhang Y (2011) Tet proteins
can convert 5-Methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Science
333:1300–1303. https://doi.org/10.1126/science.1210597
80. Ito S, Dalessio AC, Taranova OV, Hong K, Sowers LC, Zhang Y (2010) Role of Tet proteins
in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification. Nature
466:1129–1133. https://doi.org/10.1038/nature09303
81. Bachman M, Uribe-Lewis S, Yang X, Williams M, Murrell A, Balasubramanian S (2014)
5-Hydroxymethylcytosine is a predominantly stable DNA modification. Nat Chem
6:1049–1055. https://doi.org/10.1038/nchem.2064
82. Yu-Fei H, Bin-Zhong L, Zheng L, Peng L, Yang W, Qingyu T, Jianping D, Yingying J,
Zhangcheng C, Lin L, Yan S, Xiuxue L, Qing D, Chun-Xiao S, Kangling Z, Chuan H,
Guo-Liang X (2011) Tet-mediated formation of 5-carboxylcytosine and its excision by TDG
in mammalian DNA. Science 333:1303–1307. https://doi.org/10.1126/science.1229223
83. Zhang L, Lu X, Lu J, Liang H, Dai Q, Xu GL, Luo C, Jiang H, He C (2012) Thymine DNA
glycosylase specifically recognizes 5-carboxylcytosine-modified DNA. Nat Chem Biol
8:328–330. https://doi.org/10.1038/nchembio.914
84. Slupphaug G, Mol CD, Kavli B, Arvai AS, Krokan HE, Tainer JA (1996) A nucleotideflipping mechanism from the structure of human uracil–DNA glycosylase bound to DNA.
Nature 384:87
85. Kooistra SM, Helin K (2012) Molecular mechanisms and potential functions of histone
demethylases. Nat Rev Mol Cell Biol 13:297–311. https://doi.org/10.1038/nrm3327
450
M. R. H. Zwinderman et al.