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

Abstract 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-sensitive manner. We show that impaired BAF phosphorylation leads to its persistent association with centromeric heterochromatin and reinforced anchoring. We also show that, concomitant with reinforced anchoring of centromeric heterochromatin to the NE, impaired BAF phosphorylation has important functional consequences, compromising both NE integrity and heterochromatin coalescence, and disturbing mitotic progression. Altogether, our results suggest that anchoring of centromeric heterochromatin to the NE is a highly dynamic process regulated through BAF phosphorylation, and reveal the deleterious functional consequences of perturbing this dynamic regulation.