Direct effects on gene transcription revealed by global and CRISPR-targeted oxidative DNA damage

Local oxidative DNA damage at gene promoters directly represses specific genes, and this promoter-level transcriptional regulation depends partly on the DNA repair machinery, including OGG1.

• Why it matters: It remains unclear whether oxidative stress–driven gene expression changes arise from direct, local DNA oxidation and how repair pathways shape these early transcriptional responses.
• What they did: Using total RNA-Seq, the study mapped rapid gene repression/activation and read-through RNA induction after oxidative stress, then degraded endogenous OGG1 to show partial dependence; ChIP-seq for total or S5-phosphorylated RNA polymerase II assessed recruitment changes at transcription start sites.
• The result: A chemoptogenetic system targeting ROS to chosen genomic loci reproduced promoter repression, implying that local oxidative DNA damage alters promoter activity through repair-dependent mechanisms.