Transcriptional response to zebularine and mitomycin C (MMC) in wild type and ATR deficient Arabidopsis thaliana plants

Zebularine is a non-methylable cytidine analog that is used in epigenetic and cancer research. Its application has been shown to activate several transcriptionally silenced genetic elements; however, extent of this activation and other effects on the transcriptome are unknown. Here, we show that zebularine treatment induces preferentially genes associated with DNA damage repair response and this activation is strongly ATR-dependent. The set of up- and down-regulated genes after 24 h zebularine treatment is almost fully contained in the set of genes with changed transcription in response to 24 h MMC treatment. We identified only few genes that were up-regulated in common by longer (5 days) zebularine treatment and loss of epigenetic control in ddm1 mutant. Our results suggest that zebularine does not induce global activation of targets of transcriptional gene silencing and indicate previously unanticipated DNA damaging effects associated with zebularine-treatment.