Multi-omic analysis of altered transcriptome and epigenetic signatures in the UV-induced DNA damage response

Abstract

The transcription-related DNA damage response was visualized on a genome-wide scale with great spatial and temporal resolution. Upon UV irradiation, a small proportion of mature RNA transcripts undergo changes, with significant activation of DNA repair factors. Notably, an increase of chromatin accessibility is observed at the immediate early recovery phase and serves as binding sites for selective stage-specific transcription factors. Whole genome analysis of DNA methylation (5mC) delineates pervasive dynamics during DNA repair process, and hypomethylation at gene bodies and 3’UTR is accompanied by induction of DNA damage response genes. Furthermore, temporal-specific m6A RNA methylation has been defined and appears to affect DNA repair by modulation of translation. These findings provide a resource for identifying players required for transcription-coupled nucleotide excision repair and reveal insights into the epigenetic regulation of the transcriptional programs in response to genotoxic stress.