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

Research output: Contribution to journalArticleScientificpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1715-1731.e6
JournalMolecular Cell
Volume81
Issue number8
DOIs
Publication statusPublished - 15 Apr 2021
MoE publication typeA1 Journal article-refereed

Keywords

  • Cell Line, Tumor
  • Chromatin/genetics
  • Fibroblasts/physiology
  • Gene Expression Regulation/genetics
  • Genome/genetics
  • Heat-Shock Response/genetics
  • Humans
  • K562 Cells
  • Mitosis/genetics
  • Promoter Regions, Genetic/genetics
  • RNA Polymerase II/genetics
  • RNA, Messenger/genetics
  • Stress, Physiological/genetics
  • Transcription, Genetic/genetics

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