Activation-induced deaminase-coupled DNA demethylation is not crucial for the generation of induced pluripotent stem cells.

DNA methylation constitutes a major obstacle in the reprogramming of cells to pluripotency. Although little is known regarding the molecular mechanisms of DNA demethylation, activation-induced deaminase (AID), which is known to function in antibody diversification, has been implicated in DNA demethylation through a base excision repair (BER)-mediated pathway. Here we comprehensively examine the plausibility of coupled AID-BER demethylation in the generation of induced pluripotent stem cells (iPSCs) and show that AID is dispensable for reprogramming cells into iPSCs. Additionally, the overexpression of AID and other factors involved in AID-coupled DNA demethylation does not increase the efficiency of reprogramming. Moreover, BER is not likely to play a role in this process. Our results indicate that the reactivation of key genes governing the pluripotency circuitry occurs through a mechanism that is independent of deamination-coupled demethylation.