Figure 1
From: TET proteins and the control of cytosine demethylation in cancer
Regulation of DNA methylation and demethylation. DNA demethylation can occur spontaneously via the DNMT enzymes that methylated the nucleotide cytosine (5-methylcytosine, 5-mC) originally. A passive replication-dependent mechanism of DNA methylation is also possible. Several active demethylation pathways have been postulated. TET family proteins catalyze the oxidation of 5-mC into 5-hydroxymethylcytosine (5-hmC) and can further oxidize 5-hmC to 5-formylcytosine (5-fC) and 5-carboxycytosine (5-caC). 5-hmC recognition and transformation into 5-hydroxymethyluracyl (5-hmU) by activation-induced deaminase (AID) to facilitate repair by DNA glycosylase and the base-excision repair (BER) pathway is still controversial. These latter activities are also thought to process 5-fC and 5-caC into unmodified cytosine . The decarboxylases involved in this process are still to be identified. APOBEC, apolipoprotein B mRNA editing enzyme; DNMT, DNA methyltransferase; T, thymine; TDG, thymine DNA glycosylase; TET, ten-eleven translocation.