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

Vihervaara A, Mahat DB, Himanen SV, Blom MAH, Lis JT, Sistonen L

Mol. Cell 81 (8) 1715-1731.e6 [2021-04-15; online 2021-03-29]

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.

Anniina Vihervaara

SciLifeLab Fellow

PubMed 33784494

DOI 10.1016/j.molcel.2021.03.007

Crossref 10.1016/j.molcel.2021.03.007

mid: NIHMS1683466
pmc: PMC8054823
pii: S1097-2765(21)00175-1

Publications 9.5.0