Stress-Induced Transcriptional Memory Accelerates Promoter-Proximal Pause-Release and Decelerates Termination over Mitotic Divisions
Heat shock triggers an instant reprogramming of gene and enhancer transcription, but whether cells encode a memory to stress, at the level of nascent transcription, has remained unknown. Here, we measured transcriptional response to acute heat stress in unconditioned cells and in daughters of cells that had been exposed to a single or multiple heat shocks. Tracking RNA Polymerase II (Pol II) genome-wide at nucleotide-resolution revealed that cells precisely remember their transcriptional identity throughout stress, restoring Pol II distribution at gene bodies and enhancers upon recovery. However, single heat shock primed faster gene-induction in the daughter cells by increasing promoter-proximal Pol II pausing, and accelerating the pause-release. In repeatedly stressed cells, both basal and inducible transcription was refined, and pre-mRNA processing decelerated, which retained transcripts on chromatin and reduced recycling of the transcription machinery. These results mechanistically uncovered how the steps of pause-release and termination maintain transcriptional memory over mitosis.\n\nHighlights-Cell type-specific transcription precisely recovers after heat-induced reprogramming\n-Single heat shock primes genes for accelerated induction over mitotic divisions via increased promoter-proximal Pol II pausing and faster pause-release\n-Multiple heat shocks refine basal and inducible transcription over mitotic divisions to support survival of the daughter cells\n-Decelerated termination at active genes reduces recycling of Pol II to heat-activated promoters and enhancers\n-HSF1 increases the rate of promoter-proximal pause-release via distal and proximal regulatory elements