Activation-induced cytidine deaminase auto-activates and triggers aberrant gene expression

Abstract

DNA methylation is a well-characterized epigenetic landmark involved in transcriptional regulation; however, mechanisms underlying its regulation remain poorly characterized. Recent studies demonstrate that activation-induced cytidine deaminase (AID) is involved in active DNA demethylation. AID is aberrantly expressed in inflammation-associated cancers and generates point mutations; however, cellular disorders attributed to its demethylation function are largely unexplored. Here we demonstrate that ectopic AID expression perturbs tumor-related gene expression. AID (with Gadd45) activated a methylated paired box gene 5 (Pax5) reporter construct, and induced expression and association of endogenous Pax5 with the AID promoter, suggesting that aberrant AID expression triggers an auto-activation circuit to consolidate self-expression.