Figure 1.

DNA methylation and demethylation. (A) DNA methylation occurs at the fifth carbon of cytosine and leads to the formation of 5-methylcytosine (5mC); (B) DNA methylation is predominantly found at CpG sites, and is much less commonly observed at non-CpG sites, such as CpA, CpT, and CpC; and (C) 5mC can be demethylated by passive or active processes. Active DNA demethylation can occur either via oxidation or deamination. The oxidation process is carried out by Ten-Eleven-Translocation (TET) proteins, including TET1, TET2, and TET3. TETs convert 5mC into 5-hydroxymethylcytosine (5hmC), which is further changed into 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). 5caC is excised and replaced via base excision repair. 5mC and 5hmC can also be demethylated via deamination by activation induced cytidine deaminase (AID)/apolipoprotein B mRNA editing enzyme, catalytic polypeptide (APOBEC).