HP1 links centromeric heterochromatin to centromere cohesion in mammals

摘要

Heterochromatin protein-1 (HP1) is a key component of heterochromatin. Reminiscent of the cohesin complex which mediates sister-chromatid cohesion, most HP1 proteins in mammalian cells are displaced from chromosome arms during mitotic entry, whereas a pool remains at the heterochromatic centromere region. The function of HP1 at mitotic centromeres remains largely elusive. Here, we show that double knockout (DKO) of HP1 and HP1 causes defective mitosis progression and weakened centromeric cohesion. While mutating the chromoshadow domain (CSD) prevents HP1 from protecting sister-chromatid cohesion, centromeric targeting of HP1 CSD alone is sufficient to rescue the cohesion defects in HP1 DKO cells. Interestingly, HP1-dependent cohesion protection requires Haspin, an antagonist of the cohesin-releasing factor Wapl. Moreover, HP1 CSD directly binds the N-terminal region of Haspin and facilitates its centromeric localization. The need for HP1 in cohesion protection can be bypassed by centromeric targeting of Haspin or inhibiting Wapl activity. Taken together, these results reveal a redundant role for HP1 and HP1 in the protection of centromeric cohesion through promoting Haspin localization at mitotic centromeres in mammalian cells.