Phosphorylation of Barrier-to-Autointegration Factor (BAF) regulates anchoring of centromeric heterochromatin to the nuclear envelope (NE)

In eukaryotes, the spatial segregation of heterochromatin and euchromatin is key for the structural organization and function of the genome. Heterochromatin interacts with the nuclear envelope (NE) and occupies a more peripheral position than euchromatin. However, the mechanisms that govern tethering of heterochromatin to the NE are not fully understood. Here, we report that Barrier-to-Autointegration Factor (BAF), a highly conserved NE-associated protein, interacts with centromeric heterochromatin and regulates its anchoring to the NE in a phosphorylation dependent manner. We show that impaired BAF phosphorylation results in its persistent association with centromeric heterochromatin and reinforced anchoring. We also show that reinforced anchoring of centromeric heterochromatin to the NE has important functional consequences, compromising both NE integrity and heterochromatin coalescence, and disturbing mitosis progression and the assembly of functional centromeres. Altogether, our results suggest that anchoring of centromeric heterochromatin to the NE is a highly dynamic process regulated through BAF phosphorylation, and unveil the deleterious functional consequences of perturbing this dynamics. Overall design: Torras-Llort, Mònica