Abstract
SummaryEukaryotic genomes are organized within the nucleus through interactions with inner nuclear membrane (INM) proteins. How chromatin tethering to the INM is controlled in interphase and how this process contributes to subsequent mitotic nuclear envelope (NE) remodeling remains unclear. We have probed these fundamental questions using the fission yeast Schizosaccharomyces japonicus, which breaks and reforms the NE during mitosis. We show that attachments between heterochromatin and the transmembrane Lem2-Nur1 complex at the INM are remodeled in interphase by the ESCRT-III/Vps4 machinery. Failure of ESCRT-III/Vps4 to release Lem2-Nur1 from heterochromatin leads to persistent association of chromosomes with the INM throughout mitosis. At mitotic exit, such trapping of Lem2-Nur1 on heterochromatin prevents it from re-establishing nucleocytoplasmic compartmentalization. Our work identifies the Lem2-Nur1 complex as a substrate for the nuclear ESCRT machinery and explains how the dynamic tethering of chromosomes to the INM is linked to the establishment of nuclear compartmentalization.
Highlights
Chromosomes are compartmentalized within the nucleus, which is delimited by the double membrane of the nuclear envelope (NE)
The function of the Lem2 ortholog in NE resealing was later proposed to be mediated by its recruitment of the membrane remodeling complex ESCRT-III together with the AAA-ATPase Vps4 (Olmos et al, 2015; Vietri et al, 2015; Gu et al, 2017)
Combining cell biological and genetic analyses in S. japonicus with chromatin immunoprecipitation (ChIP) and in vitro reconstitution experiments, we show that the ESCRT-III/Vps4 machinery remodels attachments between Lem2 and heterochromatin during interphase
Summary
Chromosomes are compartmentalized within the nucleus, which is delimited by the double membrane of the nuclear envelope (NE). LEM-domain proteins were proposed to work together with ESCRT-III/ Vps in mediating nuclear pore complex (NPC) quality control in Saccharomyces cerevisiae (Webster et al, 2014, 2016) and maintaining NE integrity in S. pombe (Gu et al, 2017). These processes are thought to rely on the capacity of the ESCRT machinery to remodel membranes. If and how the function of Lem and ESCRT-III/Vps in establishing and maintaining nuclear compartmentalization is linked to their roles in chromatin organization remained unclear
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