VPS72/YL1-Mediated H2A.Z Deposition Is Required for Nuclear Reassembly after Mitosis.

Daniel Moreno-Andrés,Hongqi Lue,Hideki Yokoyama,Marion Weberruss,Wolfram Antonin,Masatoshi Takagi,Guillaume Holzer,Anna Katharina Schellhaus,Anja Scheufen

doi:10.3390/cells9071702

Daniel Moreno-Andrés, Hongqi Lue + Show 7 more

Open Access

https://doi.org/10.3390/cells9071702

Copy DOI

Abstract

The eukaryotic nucleus remodels extensively during mitosis. Upon mitotic entry, the nuclear envelope breaks down and chromosomes condense into rod-shaped bodies, which are captured by the spindle apparatus and segregated during anaphase. Through telophase, chromosomes decondense and the nuclear envelope reassembles, leading to a functional interphase nucleus. While the molecular processes occurring in early mitosis are intensively investigated, our knowledge about molecular mechanisms of nuclear reassembly is rather limited. Using cell free and cellular assays, we identify the histone variant H2A.Z and its chaperone VPS72/YL1 as important factors for reassembly of a functional nucleus after mitosis. Live-cell imaging shows that siRNA-mediated downregulation of VPS72 extends the telophase in HeLa cells. In vitro, depletion of VPS72 or H2A.Z results in malformed and nonfunctional nuclei. VPS72 is part of two chromatin-remodeling complexes, SRCAP and EP400. Dissecting the mechanism of nuclear reformation using cell-free assays, we, however, show that VPS72 functions outside of the SRCAP and EP400 remodeling complexes to deposit H2A.Z, which in turn is crucial for formation of a functional nucleus.

Highlights

The eukaryotic cell nucleus reorganizes considerably during cell division [1,2]
While key molecular processes directing the progression through early mitosis and chromatin segregation have been relatively well investigated, much less is known about those molecular mechanisms mediating de-condensation of mitotic chromosomes and subsequent nuclear reassembly including nuclear envelope reformation [3,4]
To shed light on the molecular mechanisms that support the action of pontin and reptin during mitotic chromatin de-condensation, we investigated pontin/reptin interacting proteins found in chromatin remodeling complexes that could act as cofactors in chromatin de-condensation

Summary

Introduction

The eukaryotic cell nucleus reorganizes considerably during cell division [1,2]. During early mitosis in metazoans, the nuclear envelope breaks down and the chromatin condenses into individualized rod-shaped chromosomes. During late anaphase and telophase, the highly condensed mitotic chromosomes decondense, reestablishing a fully functional interphase nucleus. While key molecular processes directing the progression through early mitosis and chromatin segregation have been relatively well investigated, much less is known about those molecular mechanisms mediating de-condensation of mitotic chromosomes and subsequent nuclear reassembly including nuclear envelope reformation [3,4]. Several phosphatases promote the inactivation of mitotic kinases of the Aurora family, polo-like kinase 1 (PLK1) and the cyclin dependent kinase 1 (CDK1) [5,6].

Methods

Results

Conclusion