DNA methylation is one of the earliest epigenetic modifications found in humans. It is a type of post-replication modification that often occurs in cytosines of the CpG dinucleotide sequence with the help of DNA methyltransferases (DNMTs),which transfer a methyl group from S-adenyl methionine to the fifth carbon of a cytosine residue to form 5-methylcytosine (5mC). The process of demethylation is more complex and can be passive or active. Ten-eleven translocation (TET) enzymes oxidize 5mCs and promote locus-specific removal of DNA methylation.Specifically, in the presence of water, oxygen, and α-ketoglutarate, 5mC becomes 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) through stepwise oxidation, yielding carbon dioxide and succinate.Then both 5fC and 5caC can be replaced by an unmodified cytosine through thymine DNA glycosylase-mediated base-excision repair.