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

doi:10.1016/j.molcel.2021.03.007

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

^*Tämän työn vastaava kirjoittaja

Biokemia ja solubiologia

Tutkimustuotos: Lehtiartikkeli › Artikkeli › Tieteellinen › vertaisarvioitu

36 Sitaatiot (Scopus)

179 Lataukset (Pure)

Abstrakti

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.

Alkuperäiskieli	Englanti
Sivut	1715-1731.e6
Julkaisu	Molecular Cell
Vuosikerta	81
Numero	8
DOI - pysyväislinkit	https://doi.org/10.1016/j.molcel.2021.03.007 https://doi.org/10.1016/j.molcel.2021.03.007
Tila	Julkaistu - 15 huhtik. 2021
OKM-julkaisutyyppi	A1 Julkaistu artikkeli, soviteltu

Rahoitus

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 Jusélius 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.), Åbo 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. 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.

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AuthorManuscript_Vihervaara_etal_MolCell_2021Hyväksytty kirjoittajan käsikirjoitus, 17,2 MBLisenssi: CC BY-NC-ND

https://urn.fi/URN:NBN:fi-fe2022032925712

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@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",

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TY - JOUR

T1 - Stress-induced transcriptional memory accelerates promoter-proximal pause release and decelerates termination over mitotic divisions

AU - Vihervaara, Anniina

AU - Mahat, Dig Bijay

AU - Himanen, Samu V.

AU - Blom, Malin A.H.

AU - Lis, John T.

AU - Sistonen, Lea

N1 - 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 Jusélius 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.), Åbo 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: © 2021 Elsevier Inc.

PY - 2021/4/15

Y1 - 2021/4/15

N2 - 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.

AB - 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.

KW - acquired stress resistance

KW - chromatin accessibility

KW - enhancer transcription

KW - gene-enhancer networks

KW - nascent transcription program

KW - Pol II pausing

KW - progression of Pol II

KW - recycling of Pol II

KW - transcription termination

UR - https://www.scopus.com/pages/publications/85104077746

U2 - 10.1016/j.molcel.2021.03.007

DO - 10.1016/j.molcel.2021.03.007

M3 - Article

C2 - 33784494

AN - SCOPUS:85104077746

SN - 1097-2765

VL - 81

SP - 1715-1731.e6

JO - Molecular Cell

JF - Molecular Cell

IS - 8

ER -

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

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