Cremer, Marion ; Brandstetter, Katharina ; Maiser, Andreas ; Rao, Suhas S. P. ; Schmid, Volker J. ; Guirao-Ortiz, Miguel ; Mitra, Namita ; Mamberti, Stefania ; Klein, Kyle N. ; Gilbert, David M. ; Leonhardt, Heinrich ; Cardoso, M. Cristina ; Aiden, Erez Lieberman ; Harz, Hartmann ; Cremer, Thomas (2020)
Cohesin depleted cells rebuild functional nuclear compartments after endomitosis.
In: Nature communications, 11 (1)
doi: 10.1038/s41467-020-19876-6
Artikel, Bibliographie

Kurzbeschreibung (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.

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