Stress-induced transcriptional memory accelerates promoter-proximal pause release and decelerates termination over mitotic divisions

Heat shock instantly reprograms transcription. Whether gene and enhancer transcription fully recover from stress and whether stress establishes a memory by provoking transcription regulation that persists through mitosis remained unknown. Here, we measured nascent transcription and chromatin accessibility in unconditioned cells and in the daughters of stress-exposed cells. Tracking transcription genome-wide at nucleotide-resolution revealed that cells precisely restored RNA polymerase II (Pol II) distribution at gene bodies and enhancers upon recovery from stress. However, a single heat exposure in embryonic fibroblasts primed a faster gene induction in their daughter cells by increasing promoter-proximal Pol II pausing and by accelerating the pause release. In K562 erythroleukemia cells, repeated stress refined basal and heat-induced transcription over mitotic division and decelerated termination-coupled pre-mRNA processing. The slower termination retained transcripts on the chromatin and reduced recycling of Pol II. These results demonstrate that heat-induced transcriptional memory acts through promoter-proximal pause release and pre-mRNA processing at transcription termination.

Automated summary

Heat shock rapidly reprograms transcription, but gene and enhancer transcription can fully recover from stress. The study found that cells precisely restored RNA polymerase II distribution at gene bodies and enhancers upon recovery from stress. Moreover, heat-induced transcriptional memory acts through different mechanisms in embryonic fibroblasts and K562 erythroleukemia cells, including promoting Pol II pause release and slowing down transcription termination.