biostudies-literatureAbdouni HCanadian Institutes of Health Research5457-68https://www.ebi.ac.uk/biostudies/studies/S-EPMC3664802biostudies-literatureUnknown41(10)Activation-induced cytidine deaminase (AID) deaminates deoxycytidine (dC) to deoxyuracil (dU) at immunoglobulin loci in B lymphocytes to mediate secondary antibody diversification. Recently, AID has been proposed to also mediate epigenetic reprogramming by demethylating methylated cytidines (mC) possibly through deamination. AID overexpression in zebrafish embryos was shown to promote genome demethylation through G:T lesions, implicating a deamination-dependent mechanism. We and others have previously shown that mC is a poor substrate for human AID. Here, we examined the ability of bony fish AID to deaminate mC. We report that zebrafish AID was unique among all orthologs in that it efficiently deaminates mC. Analysis of domain-swapped and mutant AID revealed that mC specificity is independNucleic acids researchZebrafish AID is capable of deaminating methylated deoxycytidines.PMC3664802MOP111132Fifield HKing JJLarijani MAbdouni HSuliman MQuinlan MfalseZebrafish AID is capable of deaminating methylated deoxycytidines.Activation-induced cytidine deaminase (AID) deaminates deoxycytidine (dC) to deoxyuracil (dU) at immunoglobulin loci in B lymphocytes to mediate secondary antibody diversification. Recently, AID has been proposed to also mediate epigenetic reprogramming by demethylating methylated cytidines (mC) possibly through deamination. AID overexpression in zebrafish embryos was shown to promote genome demethylation through G:T lesions, implicating a deamination-dependent mechanism. We and others have previously shown that mC is a poor substrate for human AID. Here, we examined the ability of bony fish AID to deaminate mC. We report that zebrafish AID was unique among all orthologs in that it efficiently deaminates mC. Analysis of domain-swapped and mutant AID revealed that mC specificity is independ2013-01-01T00:00:00Z2013 May2025-04-18T16:27:24.154Z2019-03-27T01:10:27ZS-EPMC36648022358527910.1093/nar/gkt212