Nuclear lamina maintains global spatial organization of chromatin in Drosophila cultured cells

Abstract

Interphase chromatin in animals is constrained by interactions with the nuclear lamina (NL) – a protein mesh lining nuclear envelope and composed from lamins and lamin-associated proteins. About 30% of chromatin is located near the NL in a living cell forming densely packed lamina-associated domains (LADs). LADs largely overlap with topologically-associating domains (TADs) build up from repressed chromatin, and contain predominately inactive genes, thus playing a role in transcription regulation. Here, we show that the NL disruption in Drosophila leads to en mass chromatin compactisation and redistribution towards the nuclear interior. This results in an increase of contact frequency between active and repressed fractions of the genome accompanied by the transcription upregulation in LADs. A subset of TADs characterized by high level of LADs become less compact, that could be driven by the loss of interactions with the nuclear envelope as revealed by polymer modelling. These results indicate that the NL in Drosophila cells plays a role in the specific spatial positioning of the chromatin inside the nucleus, its compartmentalization and at least partially controls the packaging density and low-level transcription in LADs.