Polycomb-group proteins mediate gene silencing as multisubunit protein complexes by modifying histone tails and altering high-order chromatin structure. Polycomb repressive complex 2 (PRC2) catalyzes tri-methylation of histone H3 at lysine 27 (H3K27me3), an epigenetic hallmark of repressed chromatin.

    PRC2 consists of four core subunits—Ezh2, Eed, Suz12, and Rbbp4. In addition, auxiliary subunits—such as Aebp2, Jarid2, and mammalian orthologs of Drosophila melanogaster polycomb- like (Pcl) protein (Phf1, Phf19, and Mtf2)—associate with the core PRC2, modulate its enzyme activity, and facilitate its recruitment to target genomic loci .

   Ten structurally and functionally discrete Ezh2 domains are dispersed across the entire active complex and compose an extended structural scaffold to accommodate juxtaposed Eed and Suz12(VEFS)
   
    The N terminus of Ezh2 forms an intramolecular interaction with the SANT1-like(SANT1L) domain.

    The Eed-binding domain(EBD) occupies a surface groove across the bottom face of he Eed WD40 domain.

    Continuation of the EBD on the side face of Eed leads to the beta-addition motif (BAM).

    Following BAM, an Ezh2 loop region migrates away from the Eed surface, extends to the back of the SET domain of the catalytic moiety. and is referred to as SET activation loop(SAL).
   
    SAL merges from between SET domain and Suz12(VEFS) to directly connect to the stimulation-responsive motif(SRM), which sits on the stimulating peptide at the center of the top face of Eed and forms a sandwich-like assembly with Eed and the H3K27me3 peptide.

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