Oxidative stress triggers rapid and reversible genome-wide RNA polymerase II stalling

Proper control of transcription is required for accurate gene expression. While it is well known that cellular stress leads to activation of stress response genes, it is less appreciated that cellular stress also can promote a global repression of transcription. In particular, the transcriptional response to oxidative stress is poorly understood. Through transcription activity profiling, we uncover a rapid and widespread reduction of global transcription following oxidative stress. By monitoring total RNAPII occupancy and elongation dynamics we established that transient oxidative stress arrests the progression of RNAPII within few minutes regardless of its position in the gene. Upon recovery, nascent transcription is rapidly restored with stalled RNAPII complexes within the gene body resuming transcription. Our data show that global transcription is dynamically affected by oxidative stress in a unique and transient manner characterised by abrupt stalling of RNAPII followed by a rapid recovery characterised by promiscuous RNAPII elongation. Interestingly, this is governed by mechanisms different from the transcriptional response to heat shock or UV irradiation but instead is controlled both by PARylation and DNA repair through the base excision repair pathway.