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Mitotic chromosome condensation resets chromatin to maintain transcriptional homeostasis

Lucía Ramos-Alonso, Petter Holland, Stéphanie Le Gras, Xu Zhao, Bernard Jost, Magnar Bjørås, View ORCID ProfileYves Barral, View ORCID ProfileJorrit M. Enserink, View ORCID ProfilePierre Chymkowitch
doi: https://doi.org/10.1101/2022.05.11.491439
Lucía Ramos-Alonso
1Department of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, 0316 Oslo, Norway
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Petter Holland
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Stéphanie Le Gras
2Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS UMR7104, Inserm U1258, Université de Strasbourg, Illkirch, France
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Xu Zhao
1Department of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, 0316 Oslo, Norway
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Bernard Jost
2Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS UMR7104, Inserm U1258, Université de Strasbourg, Illkirch, France
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Magnar Bjørås
3Department of Microbiology, Oslo University Hospital and University of Oslo, 0372 Oslo, Norway
4Department of Clinical and Molecular Medicine, NTNU; Trondheim, Norway
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Yves Barral
5Institute of Biochemistry, Biology Department, ETH Zurich, 8093 Zurich, Switzerland
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  • For correspondence: pierre.chymkowitch@ibv.uio.no j.m.enserink@ibv.uio.no yves.barral@bc.biol.ethz.ch
Jorrit M. Enserink
1Department of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, 0316 Oslo, Norway
6Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, 0372 Oslo, Norway
7Centre for Cancer Cell Reprogramming, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, 0318 Oslo, Norway
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  • For correspondence: pierre.chymkowitch@ibv.uio.no j.m.enserink@ibv.uio.no yves.barral@bc.biol.ethz.ch
Pierre Chymkowitch
1Department of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, 0316 Oslo, Norway
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  • ORCID record for Pierre Chymkowitch
  • For correspondence: pierre.chymkowitch@ibv.uio.no j.m.enserink@ibv.uio.no yves.barral@bc.biol.ethz.ch
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Abstract

Mitotic entry correlates with the condensation of the chromosomes, remodeling of histone modifications, exclusion of transcription factors from DNA and the broad downregulation of transcription. However, whether mitotic condensation influences transcription in the subsequent interphase is unknown. Here, we show that preventing one chromosome to condense during mitosis causes it to fail resetting transcription. Rather it diverted the transcription machinery and underwent unscheduled initiation of gene expression. This caused the activation of inducible transcriptional programs, such as the GAL genes, even in absence of the relevant stimuli. Strikingly, aberrant gene expression persisted into the next interphase. Thus, our study identifies the maintenance of transcriptional homeostasis as an unexpected and yet unexplored function of mitotic chromosome condensation.

One-Sentence Summary Mitotic chromatin condensation resets the transcriptome to protect cells from transcriptional drifting after anaphase.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted May 11, 2022.
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Mitotic chromosome condensation resets chromatin to maintain transcriptional homeostasis
Lucía Ramos-Alonso, Petter Holland, Stéphanie Le Gras, Xu Zhao, Bernard Jost, Magnar Bjørås, Yves Barral, Jorrit M. Enserink, Pierre Chymkowitch
bioRxiv 2022.05.11.491439; doi: https://doi.org/10.1101/2022.05.11.491439
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Mitotic chromosome condensation resets chromatin to maintain transcriptional homeostasis
Lucía Ramos-Alonso, Petter Holland, Stéphanie Le Gras, Xu Zhao, Bernard Jost, Magnar Bjørås, Yves Barral, Jorrit M. Enserink, Pierre Chymkowitch
bioRxiv 2022.05.11.491439; doi: https://doi.org/10.1101/2022.05.11.491439

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