Figure 6.

Model of Tet-initiated DNA demethylation pathways. DNA methylation (5mC) is established and maintained by DNMT. 5mC can by oxidized by Tet family of dioxygenases to generate 5hmC, 5fC, and 5caC. Because the oxidized 5mC derivatives cannot serve as substrates for DNMT1, they can be lost by replication-dependent passive demethylation. 5hmC can be deaminated by AID/APOBEC to become 5hmU, which together with 5fC and 5caC can be excised by glycosylases such as TDG, followed by DNA repair to generate C. Alternatively, a putative decarboxylase may convert 5caC to C.