MORC3 Forms Nuclear Condensates through Phase Separation

Yi Zhang; Bianca Bertulat; Adam H Tencer; Xiaojun Ren; Gregory M Wright; Joshua Black; M Cristina Cardoso; Tatiana G Kutateladze

doi:10.1016/j.isci.2019.06.030

MORC3 Forms Nuclear Condensates through Phase Separation

iScience. 2019 Jul 26:17:182-189. doi: 10.1016/j.isci.2019.06.030. Epub 2019 Jun 25.

Authors

Yi Zhang¹, Bianca Bertulat², Adam H Tencer¹, Xiaojun Ren³, Gregory M Wright¹, Joshua Black¹, M Cristina Cardoso², Tatiana G Kutateladze⁴

Affiliations

¹ Department of Pharmacology, University of Colorado School of Medicine, 12801 East 17th Avenue, Aurora, CO 80045, USA.
² Department of Biology, Technische Universität Darmstadt, Darmstadt, 64287, Germany.
³ Department of Chemistry, University of Colorado, Denver, CO 80217, USA.
⁴ Department of Pharmacology, University of Colorado School of Medicine, 12801 East 17th Avenue, Aurora, CO 80045, USA. Electronic address: tatiana.kutateladze@ucdenver.edu.

Abstract

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.

Keywords: Biological Sciences; Biophysical Chemistry; Molecular Biology.

Abstract

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