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Cohesin depleted cells rebuild functional nuclear compartments after endomitosis

Author

Listed:
  • 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
    Stanford University School 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
    Rice University
    Broad Institute of the Massachusetts Institute of Technology and Harvard University
    Rice University)

  • Hartmann Harz

    (Ludwig-Maximilians-Universität München)

  • Thomas Cremer

    (Ludwig-Maximilians-Universität München)

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.

Suggested Citation

  • 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 Leon, 2020. "Cohesin depleted cells rebuild functional nuclear compartments after endomitosis," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19876-6
    DOI: 10.1038/s41467-020-19876-6
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    Cited by:

    1. Lina Zheng & Wei Wang, 2022. "Regulation associated modules reflect 3D genome modularity associated with chromatin activity," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    2. Timothy A. Daugird & Yu Shi & Katie L. Holland & Hosein Rostamian & Zhe Liu & Luke D. Lavis & Joseph Rodriguez & Brian D. Strahl & Wesley R. Legant, 2024. "Correlative single molecule lattice light sheet imaging reveals the dynamic relationship between nucleosomes and the local chromatin environment," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    3. Mattia Conte & Ehsan Irani & Andrea M. Chiariello & Alex Abraham & Simona Bianco & Andrea Esposito & Mario Nicodemi, 2022. "Loop-extrusion and polymer phase-separation can co-exist at the single-molecule level to shape chromatin folding," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

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