Imaging chromatin dynamics reveals a novel mechanism for nuclear organisation after cell division

Re-establishment of nuclear structure and chromatin organisation after cell division is integral for genome regulation and cell function. However, the mechanisms underlying this process remain incompletely understood. Given the dramatic re-organisation of the nucleus during and after mitosis, we hypothesised that nuclear organisation after mitosis may be driven by filamentous structures such as polymerised actin (F-actin). Accordingly and by using multiple approaches for visualising actin polymerisation, we discovered a transient and pronounced assembly of F-actin in the nuclei of daughter cells upon exiting mitosis. By developing a quantitative method for imaging chromatin dynamics in intact cell using florescent lifetime imaging microscopy (FLIM), we identified a key role for this F-actin in chromatin de-condensation after mitosis. This is further supported by visualisation of chromatin organisation using electron microscopy. A combination of quantitative biochemical and cell imaging assays revealed that chemical or genetic interference with this nuclear F-actin assembly impairs the re-establishment of nuclear structure and chromatin organisation post mitosis, and influences transcription and replication in the daughter cells. These findings identify a novel spatiotemporally controlled form of nuclear F-actin that contributes to the chromatin organization in mammalian somatic after cell division, with potential implications for regulating chromatin structure and function in the context of the cell cycle.