Figure 2.
Proposed DNA demethylation pathways that involve 5hmC. DNA methylation (5mC) is established and maintained by DNA methyltransferases (DNMTs). In mammals, 5mC can be oxidized by the Tet proteins to generate 5hmC. 5hmC is recognized poorly by Dnmt1 and can be diluted during DNA replication. 5hmC can also be further oxidized by Tet proteins to produce 5fC and 5caC. Alternatively, 5hmC may be deaminated by AID/APOBECs to become 5hmU. 5fC, 5caC, and 5hmU can be excised from DNA by glycosylases. In addition, DNMT3A and DNMT3B may directly dehydroxymethylate 5hmC to generate unmodified C. Note that solid lines represent processes with strong evidence, while the dashed lines indicate processes which need to be further confirmed controversial process.