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. Author manuscript; available in PMC: 2015 Aug 1.
Published in final edited form as: Exp Hematol. 2014 Jun 30;42(8):609–617. doi: 10.1016/j.exphem.2014.04.008

Figure 1. The DNA methylation and demethylation pathway.

Figure 1

Overview of the DNA methylation and demethylation process. Dnmt1 is responsible for maintenance methylation. A)Dnmt1 adds methylation to hemi-methylated DNA when one strand is already methylated. Dnmt3a and Dnmt3b are responsible for de novo DNA methylation. They create hemi-methylated CpG dinucleotides to establish new patterns of methylation. B) Passive demethylation occurs through loss of Dnmt1/3 (via loss of gene expression, gene mutation, or possibly via other mechanisms that inhibit protein function). Active demethylation is mediated by Tet family proteins. 5-methylcytosine (5mC) can be hydroxylated to 5-hydroxymethylcytosine (5hmC) by Tet proteins. 5hmC is not recognized by the maintenance methyltransferase (Dnmt1), so the methylated is lost during DNA replication. In addition, 5hmC can be further oxidized to 5-formylcytosines (5fC) and 5-carboxylcytosines (5caC). These latter forms may be removed by base-excision repair, in an alternate mode of active demethylation (in addition to loss of the 5hmC by cell division).