Activation-induced cytidine deaminase and active cytidine demethylation

•Activation-induced deaminase (AID) could potentially trigger DNA demethylation.•Published reports on genome-wide AID-mediated demethylation are conflicting.•Substantial evidence supports a role for AID in gene-specific demethylation.

The regulation of demethylation in vertebrates has begun to be elucidated in the past decade. However, a possible involvement of activation-induced cytidine deaminase (AID) in this process remains uncertain. We survey the data supporting or casting doubt on such a role, and propose that there is no strong evidence for an involvement of AID in genome-wide active demethylation processes. Conversely, we present evidence that favors AID involvement in gene-specific demethylation events underlying cell differentiation.