@article{9a0fcd8e014c460bbd1d671e2b0500da,
title = "Stress-induced transcriptional memory accelerates promoter-proximal pause release and decelerates termination over mitotic divisions",
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.",
keywords = "acquired stress resistance, chromatin accessibility, enhancer transcription, gene-enhancer networks, nascent transcription program, Pol II pausing, progression of Pol II, recycling of Pol II, transcription termination",
author = "Anniina Vihervaara and Mahat, {Dig Bijay} and Himanen, {Samu V.} and Blom, {Malin A.H.} and Lis, {John T.} and Lea Sistonen",
note = "Funding Information: We thank the members of the Sistonen and the Lis laboratories for valuable advice during the manuscript preparation. This work was financially supported by the Sigrid Jus{\'e}lius Foundation (A.V. and L.S.), Academy of Finland (A.V. and L.S.), SciLifeLab (A.V.), Svenska Tekniska Vetenskapsakademin i Finland (A.V.), South-West Finland{\textquoteright}s Cancer Foundation (A.V.), Borg Memory Foundation (A.V.), {\AA}bo Akademi University (A.V. and L.S.), The Finnish Cultural Foundation (A.V.), Alfred Kordelin Foundation (S.V.H.), Cancer Foundation Finland (L.S.), Magnus Ehrnrooth Foundation (L.S.), and NIH grants RO1-GM25232 and HG009393 (J.T.L.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Funding Information: We thank the members of the Sistonen and the Lis laboratories for valuable advice during the manuscript preparation. This work was financially supported by the Sigrid Jus?lius Foundation (A.V. and L.S.), Academy of Finland (A.V. and L.S.), SciLifeLab (A.V.), Svenska Tekniska Vetenskapsakademin i Finland (A.V.), South-West Finland's Cancer Foundation (A.V.), Borg Memory Foundation (A.V.), ?bo Akademi University (A.V. and L.S.), The Finnish Cultural Foundation (A.V.), Alfred Kordelin Foundation (S.V.H.), Cancer Foundation Finland (L.S.), Magnus Ehrnrooth Foundation (L.S.), and NIH grants RO1-GM25232 and HG009393 (J.T.L.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. A.V. J.T.L. and L.S. conceived and designed the study. A.V. D.B.M. S.V.H. and M.A.H.B. conducted the laboratory work, and A.V. and D.B.M. performed the computational data analyses. All the authors interpreted the results. A.V. J.T.L. and L.S. wrote the manuscript with edits from D.B.M. S.V.H. and M.A.H.B. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",
year = "2021",
month = apr,
day = "15",
doi = "10.1016/j.molcel.2021.03.007",
language = "English",
volume = "81",
pages = "1715--1731.e6",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "8",
}