DNA methylation pathway. DNA methylation occurs on the C5 position of cytosine to form 5mC and is catalyzed by the family of DNA methyltransferases that includes DNMT3A. Active demethylation is catalyzed by TET enzymes, which are oxygen-, α-KG–, and vitamin C (VitC)–dependent dioxygenases. Demethylation proceeds through iterative oxidation of 5mC to 5hmC, 5-formylcytosine, and 5-carboxylcytosine. Final replacement with unmethylated cytosines is mediated by thymine DNA glycosylase (TDG) and the base excision repair (BER) pathway. Passive DNA demethylation occurs through inadequate methylation maintenance after DNA replication. Professional illustration by Somersault18:24.