%0 Journal Article %A Pieper, Gerard H. %A Sprenger, Simon %A Teis, David %A Oliferenko, Snezhana %T ESCRT-III/Vps4 controls heterochromatin-nuclear envelope attachments %D 2019 %R 10.1101/579805 %J bioRxiv %P 579805 %X In eukaryotes chromosomes are compartmentalized within the nucleus delimited by the double membrane of the nuclear envelope (NE). Defects in the function and structure of the NE are linked to disease1,2. During interphase, the NE organizes the genome and regulates its expression3. As cells enter mitosis, chromosomes are released from the NE, which is then remodelled to form the daughter nuclei at mitotic exit4. Interactions between the NE and chromatin underpinning both interphase and post-mitotic NE functions are executed by inner nuclear membrane (INM) proteins such as members of the evolutionarily conserved chromatin-binding LEM-domain family5–8. How chromatin tethering by these transmembrane proteins is controlled in interphase and if such a regulation contributes to subsequent NE dynamics in mitosis remains unclear. Here we probe these fundamental questions using an emerging model organism, the fission yeast Schizosaccharomyces japonicus, which breaks and reforms the NE during mitosis9,10. We show that attachments between heterochromatin and the transmembrane Lem2-Nur1 complex are continuously remodelled in interphase by the ESCRT-III/AAA-ATPase Vps4 machinery. ESCRT-III/Vps4 mediates the release of Lem2-Nur1 from heterochromatin as a prerequisite for the timely progression through mitosis. Failure in this process leads to persistent association of chromosomes with the INM, which prevents Lem2-Nur1 from re-localizing to the sites of NE sealing around the mitotic spindle and severely delays re-establishment of nucleocytoplasmic compartmentalization. Our work establishes the INM transmembrane Lem2-Nur1 complex as a ‘substrate’ for ESCRT-III/Vps4 to couple dynamic tethering of chromosomes to the INM with the establishment of nuclear compartmentalization. %U https://www.biorxiv.org/content/biorxiv/early/2019/03/15/579805.full.pdf