CBX7C⋅PHC2 interaction facilitates PRC1 assembly and modulates its phase separation properties.

CBX7 is a key component of PRC1 complex. Cbx7C is an uncharacterized Cbx7 splicing isoform specifically expressed in mouse embryonic stem cells (mESCs). We demonstrate that CBX7C functions as an epigenetic repressor at the classic PRC1 targets in mESCs, and its preferential interaction to PHC2 facilitates PRC1 assembly. Both Cbx7C and Phc2 are significantly upregulated during cell differentiation, and knockdown of Cbx7C abolishes the differentiation of mESCs to embryoid bodies. Interestingly, CBX7C⋅PHC2 interaction at low levels efficiently undergoes the formation of functional Polycomb bodies with high mobility, whereas the coordination of the two factors at high doses results in the formation of large, low-mobility, chromatin-free aggregates. Overall, these findings uncover the unique roles and molecular basis of the CBX7C⋅PHC2 interaction in PRC1 assembly on chromatin and Pc body formation and open a new avenue of controlling PRC1 activities via modulation of its phase separation properties.