Mapping early PRC2 nucleation sites upon Suz12 reintroduction reveals features of de novo Polycomb recruitment

Polycomb domains safeguard cell identity by maintaining lineage-specific chromatin states enriched in repressive histone modifications preserving the epigenetic memory of each cell lineage. While Polycomb Repressive Complex 2 (PRC2) can re-establish its occupancy after perturbation, the mechanisms that guide de novo Poly-comb recruitment remain unclear. To address this, we engineered an auxin-inducible degradation system to reversibly deplete and reintroduce the endogenous PRC2 core subunit Suz12 in mouse embryonic stem cells (mESCs). Genome-wide profiling at early recovery time point revealed PRC2 nucleation sites, characterized by rapid Suz12 and H3K27me3 re-accumulation and signal strength.