Cryo-EM structure, enzymatic activity and genome targeting of canonical PRC1

We report the cryo–electron microscopy structure of tetrameric human cPRC1 bound to a nucleosome in complex with the ubiquitin-conjugating enzyme UBCH5C. cPRC1 adopts a compact, highly integrated architecture in which the subunits RING1B, BMI1, and PHC2 form an extended interface that positions UBCH5C on the nucleosome to enable efficient monoubiquitination of histone H2A at lysine 119.

This organization is conserved in Drosophila, where mutational analyses identify the PHC2 ortholog Polyhomeotic (Ph) as a central scaffold and targeting factor. The Ph HD domain is required for complex assembly, whereas the Ph SAM domain is dispensable for assembly but essential for cPRC1 recruitment to Polycomb target genes and productive H2A monoubiquitination at these loci.