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Cohesin depleted cells rebuild functional nuclear compartments after endomitosis

Marion Cremer (), Katharina Brandstetter, Andreas Maiser, Suhas S. P. Rao, Volker J. Schmid, Miguel Guirao-Ortiz, Namita Mitra, Stefania Mamberti, Kyle N. Klein, David M. Gilbert, Heinrich Leonhardt, M. Cristina Cardoso, Erez Lieberman Aiden, Hartmann Harz () and Thomas Cremer ()
Additional contact information
Marion Cremer: Ludwig-Maximilians-Universität München
Katharina Brandstetter: Ludwig-Maximilians-Universität München
Andreas Maiser: Ludwig-Maximilians-Universität München
Suhas S. P. Rao: Baylor College of Medicine
Volker J. Schmid: Ludwig-Maximilians-Universität München
Miguel Guirao-Ortiz: Ludwig-Maximilians-Universität München
Namita Mitra: Baylor College of Medicine
Stefania Mamberti: Technische Universität Darmstadt
Kyle N. Klein: Florida State University
David M. Gilbert: Florida State University
Heinrich Leonhardt: Ludwig-Maximilians-Universität München
M. Cristina Cardoso: Technische Universität Darmstadt
Erez Lieberman Aiden: Baylor College of Medicine
Hartmann Harz: Ludwig-Maximilians-Universität München
Thomas Cremer: Ludwig-Maximilians-Universität München

Nature Communications, 2020, vol. 11, issue 1, 1-16

Abstract: Abstract Cohesin plays an essential role in chromatin loop extrusion, but its impact on a compartmentalized nuclear architecture, linked to nuclear functions, is less well understood. Using live-cell and super-resolved 3D microscopy, here we find that cohesin depletion in a human colon cancer derived cell line results in endomitosis and a single multilobulated nucleus with chromosome territories pervaded by interchromatin channels. Chromosome territories contain chromatin domain clusters with a zonal organization of repressed chromatin domains in the interior and transcriptionally competent domains located at the periphery. These clusters form microscopically defined, active and inactive compartments, which likely correspond to A/B compartments, which are detected with ensemble Hi-C. Splicing speckles are observed nearby within the lining channel system. We further observe that the multilobulated nuclei, despite continuous absence of cohesin, pass through S-phase with typical spatio-temporal patterns of replication domains. Evidence for structural changes of these domains compared to controls suggests that cohesin is required for their full integrity.

Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19876-6

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DOI: 10.1038/s41467-020-19876-6

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