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

: Vihervaara Anniina, Mahat Dig Bijay, Himanen Samu V, Blom Malin AH, Lis John T, Sistonen Lea

Publisher: CELL PRESS

: 2021

: Molecular Cell

: MOLECULAR CELL

: MOL CELL

: 81

: 8

: 1715

: 1731

: 23

: 1097-2765

: 1097-4164

DOI: https://doi.org/10.1016/j.molcel.2021.03.007

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.