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

Anniina Vihervaara*, Dig Bijay Mahat, Samu V. Himanen, Malin A.H. Blom, John T. Lis, Lea Sistonen

*Korresponderande författare för detta arbete

Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

14 Citeringar (Scopus)
7 Nedladdningar (Pure)

Sammanfattning

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.

OriginalspråkEngelska
Sidor (från-till)1715-1731.e6
TidskriftMolecular Cell
Volym81
Nummer8
DOI
StatusPublicerad - 15 apr. 2021
MoE-publikationstypA1 Tidskriftsartikel-refererad

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