Species-specific satellite DNA composition dictates de novo formation of PRC1-mediated pericentric heterochromatin

Pericentromeres are heterochromatic regions adjacent to centromeres that ensure accurate chromosome segregation. Despite their conserved function, they are composed of rapidly evolving A/T-rich satellite DNA. This paradoxical observation is partially resolved by epigenetic mechanisms that maintain heterochromatin, independent of specific DNA sequences. However, it is unclear how satellite DNA sequence variation impacts de novo formation of pericentric heterochromatin, which is initially absent from paternal chromosomes in the zygote. Here we show that satellite variation has functional consequences for zygotic heterochromatin formation, recruitment of the Chromosome Passenger Complex (CPC), and interactions with spindle microtubules. In M. musculus zygotes, Polycomb Repressive Complex 1 (PRC1) is recruited to pericentric satellites by its AT-hook domain, which binds runs of A/T nucleotides, to generate H2AK119ub1 (H2Aub) heterochromatin. By fertilizing M. musculus eggs with sperm from other mouse species, we show that species-specific satellite sequences differ in their ability to recruit PRC1 and form H2Aub. This satellite-DNA mediated increase in PRC1 heterochromatin leads to reduced CPC recruitment and increased microtubule forces on kinetochores. Our results provide a direct link between satellite DNA composition and pericentromere function in the zygote, when epigenetic pathways maintaining pericentromere heterochromatin are absent.