TET1,2,3 oxidizes 5-methylcytosine to 5-hydroxymethylcytosine

TET1, TET2, and TET3 each oxidize the 5-methyl group of 5-methylcytosine (5-mC) in DNA using molecular oxygen and 2-oxoglutarate as substrates and Fe(II) as a cofactor to yield 5-hydroxymethylcytosine (5-hmC), carbon dioxide, and succinate (Tahiliani et al. 2009, inferred from mouse in Ito et al. 2010). As inferred from mouse, sodium ascorbate (vitamin C) is required for full activity of these enzymes, presumably to maintain the ferrous state of iron (Fe2+) by acting as a reducing agent (Blaschke et al. 2013, Minor et al., 2013). The crystal structure of TET2 indicates that it binds specifically to 5-mC in CG dinucleotides and flips the base out of the helix into proximity of the catalytic Fe(II) where it is oxidized (Hu et al. 2013). TET3 is expressed in murine oocytes and zygotes and is implicated in demethylation of the male pronucleus after fertilization (Iqbal et al. 2011). As inferred from mouse, TET1 and TET2 appear to participate in differentiation of stem cells. TET1,TET2, and TET3 are involved in establishing the increased level of 5-hmC that is characteristic of adult neurons (Guo et al. 2011, inferred from mouse in Hahn et al. 2013). TET2 is expressed in hematopoietic cells where it appears to act as a tumor suppressor (Ko et al. 2010).

TET1、TET2及TET3分别利用分子氧和2-氧代戊二酸作为底物，以Fe(II)作为辅因子，氧化DNA中的5-甲基胞嘧啶（5-mC）生成5-羟甲基胞嘧啶（5-hmC）、二氧化碳和琥珀酸（Tahiliani等，2009年，据Ito等，2010年对小鼠的研究推断）。据小鼠研究推断，抗坏血酸钠（维生素C）对于这些酶的完全活性是必需的，推测其作用可能在于作为还原剂维持铁的亚铁状态（Fe2+）（Blaschke等，2013年，Minor等，2013年）。TET2的晶体结构表明，它特异性地结合于CG二核苷酸中的5-mC，并将碱基从螺旋中翻转出来，进入邻近催化Fe(II)的位置，在那里进行氧化（Hu等，2013年）。TET3在鼠类卵母细胞和合子中表达，并涉嫌在受精后去除雄性原核的甲基化（Iqbal等，2011年）。据小鼠研究推断，TET1和TET2似乎参与干细胞的分化。TET1、TET2和TET3参与建立成年神经元特征性的5-hmC水平增加（Guo等，2011年，据Hahn等，2013年对小鼠的研究推断）。TET2在造血细胞中表达，似乎作为肿瘤抑制因子发挥作用（Ko等，2010年）。