MORC3 Forms Nuclear Condensates through Phase Separation

Phase separation can produce local structures with specific functionality in the cell, and in the nucleus, this can lead to chromatin reorganization. Microrchidia 3 (MORC3) is a human ATPase that has been implicated in autoimmune disorders and cancer. Here, we show that MORC3 forms phase-separated condensates with liquid-like properties in the cell nucleus. Fluorescence live-cell imaging reveals that the MORC3 condensates are heterogeneous and undergo dynamic morphological changes during the cell cycle. The ATPase activity of MORC3 drives its phase separation in vitro and requires DNA binding and releasing the MORC3 CW domain-dependent autoinhibition through association with histone H3. Our findings suggest a mechanism by which the ATPase function of MORC3 mediates MORC3 nuclear compartmentalization.