Fig. 2: DNA methylation pathway and regulation.
From: Epigenetic regulators in cancer therapy and progression
The steps involved in DNA methylation, active demethylation, and passive demethylation are depicted in this diagram. DNMT3A and DNMT3B catalyze de novo methylation, which creates new methylation patterns by converting cytosine to 5-methylcytosine. DNMT1 mediates methylation maintenance, which guarantees that 5-methylcytosine is preserved throughout DNA replication. Ten-eleven translocation (TET) enzymes oxidize 5-methylcytosine step-by-step during active demethylation, producing intermediates such 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine. Thymine DNA glycosylase (TDG) then breaks down these intermediates to restore unmethylated cytosine. When maintenance methylation is unsuccessful, methylation gradually disappears across cell divisions, a process known as passive demethylation. Both gene expression and epigenetic stability are regulated by this dynamic interaction.
