TET(ten-eleven translocation)家族蛋白是DNA主动去甲基化的关键酶,包括TET1、TET2和TET3。这些酶能够氧化5-甲基胞嘧啶(5mC)生成5-羟甲基胞嘧啶(5hmC)、5-醛基胞嘧啶(5fC)和5-羧基胞嘧啶(5caC)。这些3氧化产物可以被胸腺嘧啶DNA糖苷酶(TDG)识别并切除,随后通过碱基切除修复(BER)途径实现DNA的去甲基化。
其他可能的去甲基化途径
在小鼠胚胎发育过程中,基因组会发生两次大规模去甲基化,分别在受精后和配子形成过程中。这些去甲基化过程对于基因组重编程和胚胎发育至关重要。
细胞分化与DNA去甲基化
在细胞分化过程中,特定基因的去甲基化与基因激活相关,而甲基化则与基因沉默相关。TET酶和5hmC水平的变化与细胞多能性和分化状态密切相关。
随着衰老,全基因组或特定位点的DNA甲基化水平会发生改变,这些改变与衰老相关疾病的发展有关。
参考文献
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