Cohesin depleted cells rebuild functional nuclear compartments after endomitosis

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 und Cremer, Thomas (2020): Cohesin depleted cells rebuild functional nuclear compartments after endomitosis. In: Nature Communications, Bd. 11, Nr. 1, 6146

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Biologie
• Themengebiete: 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften; Biologie
• ISSN: 2041-1723
• Sprache: Englisch