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

Vihervaara, AnniinaKTH,Genteknologi,Science for Life Laboratory, SciLifeLab,Abo Akad Univ, Fac Sci & Engn, Cell Biol, Turku 20520, Finland.;Univ Turku, Turku Biosci Ctr, Turku 20520, Finland.;Abo Akad Univ, Turku 20520, Finland.;Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY 14853 USA. (författare)

QC 20210601
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.

Mahat, Dig BijayCornell Univ, Dept Mol Biol & Genet, Ithaca, NY 14853 USA.;MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA. (författare)
Himanen, Samu, VAbo Akad Univ, Fac Sci & Engn, Cell Biol, Turku 20520, Finland.;Univ Turku, Turku Biosci Ctr, Turku 20520, Finland.;Abo Akad Univ, Turku 20520, Finland. (författare)
Blom, Malin A. H.Abo Akad Univ, Fac Sci & Engn, Cell Biol, Turku 20520, Finland.;Univ Turku, Turku Biosci Ctr, Turku 20520, Finland.;Abo Akad Univ, Turku 20520, Finland. (författare)
Lis, John T.Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY 14853 USA. (författare)
Sistonen, LeaAbo Akad Univ, Fac Sci & Engn, Cell Biol, Turku 20520, Finland.;Univ Turku, Turku Biosci Ctr, Turku 20520, Finland.;Abo Akad Univ, Turku 20520, Finland. (författare)
KTHGenteknologi (creator_code:org_t)

Av författaren/redakt...: Vihervaara, Anni ...; Mahat, Dig Bijay; Himanen, Samu, V; Blom, Malin A. H ...; Lis, John T.; Sistonen, Lea

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