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. Author manuscript; available in PMC: 2015 Nov 3.
Published in final edited form as: Cold Spring Harb Symp Quant Biol. 2014 Mar 11;78:1–10. doi: 10.1101/sqb.2013.78.020248

Figure 2.

Figure 2

The cycle of DNA demethylation by TET proteins and the generation of oxi-mCs. DNA methyltransferases (DNMTs) add a methyl group to the 5 position of cytosine, and thus are responsible for DNA methylation. DNA demethylation can occur passively by inhibition of the maintenance methyltransferase DNMT1, especially in the presence of oxi-mCs which inhibit DNMT1, resulting in dilution of the methyl mark during replication. TET proteins in the presence of 2-oxoglutarate (OG) can oxidize mC to 5hmC, which is further oxidized by the TET proteins to 5fC and 5caC, which are much less abundant than 5hmC in the genome. 5fC and 5caC are recognized and excised by thymine DNA glycosylase (TDG) and subsequently replaced through base excision repair with unmethylated C. 5hmC has also been suggested to be directly demethylated by deamination through AID, followed by base excision repair mediated by TDG. Notably, the oxi-mCs (5hmC, 5fC and 5caC) can exert functions beyond mediating DNA demethylation, acting as marks that recruit chromatin-bound regulatory proteins.