Cbx2 Targets PRC1 to Constitutive Heterochromatin in Mouse Zygotes in a Parent-of-Origin-Dependent Manner

Polycomb repressive complexes PRC1 and PRC2 regulate expression of genes involved in proliferation and development. In mouse early embryos, however, canonical PRC1 localizes to paternal pericentric heterochromatin (pat-PCH), where it represses transcription of major satellite repeats. In contrast, maternal PCH (mat-PCH) is enriched for H3 lysine 9 tri-methylation (H3K9me3) and Hp1 beta. How PRC1 is targeted to pat-PCH, yet excluded from mat-PCH, has remained elusive. Here, we identify a PRC1 targeting mechanism that relies on Cbx2 and Hp1 beta. Cbx2 directs catalytically active PRC1 to PCH via its chromodomain (CDCbx2) and neighboring AT-hook (AT(Cbx2)) binding to H3K27me3 and AT-rich major satellites, respectively. CDCbx2 prevents AT(Cbx2) from interacting with DNA at PCH marked by H3K9me3 and Hp1 beta. Loss-of-function studies show that Hp1 beta and not H3K9me3 prevents PRC1 targeting to mat-PCH. Our findings indicate that CDCbx2 and AT(Cbx2) separated by a short linker function together to integrate H3K9me3/HP1 and H3K27me3 states.