SAF-A/HNRNPU regulates euchromatin dynamics and is required for nuclear envelope integrity

Defects in nuclear morphology are associated with cancer and premature ageing. Nuclear morphology is established by a balance of external forces produced by actin contractility and resistance provided by chromatin and the nuclear lamina. Euchromatin is decompacted to facilitate transcription, which has been shown to decrease local nucleosome motion. However, the role of transcription and euchromatic chromatin structure in nuclear envelope integrity are not clear. Here, we demonstrate that acute depletion of SAF-A/hnRNPU causes compaction of euchromatic regions and constriction of chromatin mobility, leading to loss of nuclear envelope integrity in a transcription-dependent manner. SAF-A is required in a dose-dependent manner to preserve nuclear shape under conditions of nuclear softening and elevated transcription. Our work identifies SAF-A as a dynamic scaffold that regulates chromatin structure and dynamics at sites of active transcription to preserve nuclear envelope mechanical tension.