Cohesin depleted cells rebuild functional nuclear compartments after endomitosis

Cohesin plays an essential role in chromatin loop extrusion, but its
impact on a compartmentalized nuclear architecture is debatable. Using
live-cell and super-resolved 3D microscopy, we demonstrate that
cohesin-depleted cells pass through an endomitosis and rebuild a single
multilobulated nucleus (MLN) with chromosome territories (CTs) pervaded by
interchromatin channels. CTs contain chromatin domain clusters with a
zonal organization of repressed chromatin domains in the interior and
transcriptionally competent domains located at the periphery. Splicing
speckles are located nearby within the lining channel system. These
clusters form microscopically defined, active and inactive compartments,
which correspond to A and B compartments, respectively, in ensemble Hi-C.
Functionality of MLN despite continuous absence of cohesin was
demonstrated by their ability to 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.