A fraction of barrier-to-autointegration factor (BAF) associates with centromeres and controls mitosis progression

Mònica Torras-Llort,Marcin R Przewloka,Sònia Medina-Giró,Zoltan Lipinszki,Fernando Azorín,Paula Escudero-Ferruz,Zoltan Karman,Olga Moreno-Moreno

doi:10.1038/s42003-020-01182-y

Abstract

Barrier-to-Autointegration Factor (BAF) is a conserved nuclear envelope (NE) component that binds chromatin and helps its anchoring to the NE. Cycles of phosphorylation and dephosphorylation control BAF function. Entering mitosis, phosphorylation releases BAF from chromatin and facilitates NE-disassembly. At mitotic exit, PP2A-mediated dephosphorylation restores chromatin binding and nucleates NE-reassembly. Here, we show that in Drosophila a small fraction of BAF (cenBAF) associates with centromeres. We also find that PP4 phosphatase, which is recruited to centromeres by CENP-C, prevents phosphorylation and release of cenBAF during mitosis. cenBAF is necessary for proper centromere assembly and accurate chromosome segregation, being critical for mitosis progression. Disrupting cenBAF localization prevents PP2A inactivation in mitosis compromising global BAF phosphorylation, which in turn leads to its persistent association with chromatin, delays anaphase onset and causes NE defects. These results suggest that, together with PP4 and CENP-C, cenBAF forms a centromere-based mechanism that controls chromosome segregation and mitosis progression.

Highlights

Barrier-to-Autointegration Factor (BAF) is a conserved nuclear envelope (NE) component that binds chromatin and helps its anchoring to the NE
Others and we identified BAF amongst the proteins co-purifying with centromeric chromatin enriched in the histone H3 variant CENP-ACID25 (Supplementary Table 1)
In interphase cells, we observed that BAF preferentially associated with heterochromatin, since it strongly co-localized with the heterochromatic HP1a variant (Fig. 1a, left), being largely excluded from regions enriched in the euchromatic HP1c isoform (Fig. 1a, center)

Summary

Introduction

Barrier-to-Autointegration Factor (BAF) is a conserved nuclear envelope (NE) component that binds chromatin and helps its anchoring to the NE. Disrupting cenBAF localization prevents PP2A inactivation in mitosis compromising global BAF phosphorylation, which in turn leads to its persistent association with chromatin, delays anaphase onset and causes NE defects. These results suggest that, together with PP4 and CENP-C, cenBAF forms a centromere-based mechanism that controls chromosome segregation and mitosis progression. Together with PP4/Flfl and CENP-C, cenBAF forms a centromeric network that controls phosphorylation and association with chromatin of the bulk of BAF, and regulates mitosis progression

Methods

Results

Conclusion