Figure 1.

DNA demethylation and methylation: DNAm in eukaryotes occurs mainly at cytosine’s fifth carbon atom, catalyzed by de novo methyltransferases (DNMT). Active DNA demethylation involves the successive oxidation of the 5-methyl-cytosine (5-mC) to 5-hydroxymethyl-cytosine (5-hmC), to 5-formyl-cytosine (5-fC), and then to 5-carboxy- cytosine (5-caC), catalyzed by the Ten-eleven translocation enzyme family (Tet). Passive DNA demethylation occurs during replication due to the absence of methylation by DNMT1 across several rounds of replication. Figure by Gabriela Olivares-Castro [59,60].