Molecular basis of PRC1 targeting to Polycomb response elements by PhoRC

Polycomb group (PcG) protein complexes repress transcription by modifying target gene chromatin. In Drosophila, this repression requires association of PcG protein complexes with cis-regulatory Polycomb response elements (PREs), but the interactions permitting formation of these assemblies are poorly understood. We show that the Sfmbt subunit of the DNA-binding Pho-repressive complex (PhoRC) and the Scm subunit of the canonical Polycomb-repressive complex 1 (PRC1) directly bind each other through their SAM domains. The 1.9 angstrom crystal structure of the Scm-SAM: Sfmbt-SAM complex reveals the recognition mechanism and shows that Sfmbt-SAM lacks the polymerization capacity of the SAM domains of Scm and its PRC1 partner subunit, Ph. Functional analyses in Drosophila demonstrate that Sfmbt-SAM and Scm-SAM are essential for repression and that PhoRC DNA binding is critical to initiate PRC1 association with PREs. Together, this suggests that PRE-tethered Sfmbt-SAM nucleates PRC1 recruitment and that Scm-SAM/Ph-SAM-mediated polymerization then results in the formation of PRC1-compacted chromatin.