Abstract
Polycomb repressive complexes PRC1 and PRC2 control lineage-specific gene silencing during early embryogenesis. To better understand Polycomb biology, we profile the proximal interactome (proxeome) of multiple PRC1 and PRC2 subunits in mouse embryonic stem cells (mESCs). This analysis identifies >100 proteins proximal to PRC1 and PRC2, including transcription factors and RNA-binding proteins. Notably, approximately half of the PRC2 interactors overlap with PRC1. Pluripotency-associated factors, including NANOG, colocalize with PRC2 at specific genomic sites. Following PRC2 disruption, NANOG relocalizes to other genomic regions. Interestingly, we identify PRC1 members in PRC2 proxeomes but not reciprocally. This suggests that PRC1 and PRC2 may have independent functions in addition to their cooperative roles in establishing H3K27me3-marked chromatin domains. Finally, we compare PRC2 proxeomes across different cellular contexts, including ground-state mESCs, serum-cultured mESCs, and embryoid bodies. These analyses provide a comprehensive resource, enhancing our understanding of Polycomb biology and its dynamic role across developmental states.