DNA methylation and demethylation. DNA methylation and demethylation. Representation of DNA methylation: The addition of a methyl group at the fifth carbon position of the cytosine base. This process is mediated by the DNA methyltransferase (DNMT) enzyme family. DNA demethylation is mediated by the ten eleven translocation (TET) enzyme family. Active demethylation is a sequential process in which 5-methylcytosine is converted to 5-hydroxymethylcytosine (5-hmC), which is converted to 5-formylcytosine (5-fC) and finally 5-carboxylcytosine (5-caC). This process readies the sites for thymine-DNA glycosylase (TDG) to remove both 5-fC and 5-caC. BER, base excision repair; OG, oxoglutarate; SAH, S-adenosyl-L-homocysteine; SAM, S-adenosyl-L-methionine. Adapted with permission from Martin et al.105 Cristina M Lanata et al. Lupus Sci Med 2018;5:e000285 ©2018 by Lupus Foundation of America