PRC2 is likely responsible for H3K27 mono, di and tri- methylation.

    EZH2 requires EED and SUZ12-VEFS partners to form a catalytically competent complex. The PRC2 structure suggests that EED and SUZ12-VEFS play the role of allosteric effectors in activating the SET domain.
   The structuring of activation loop by EED may induce a conformational change in the I-SET region, rendering cofactor as well as inhibitor recognition possible.

   Activation loop of EZH2, located in the N-terminal half of the primary sequence is brought into the proximity of the C-terminal SET domain largely through its interaction with EED.
    EZH2 residues wrap around EED, the activation loop is brought into the proximity of the SET domain. It may sterically induce I-SET into its observed confermation. This result in the rigid body twisting motion of the I-SET. The backbone-mediated specific hydrogen-bond interactions between the SET domain and the activation loop preclude the need for the sequence conservation in these regions, consistent with the observation of structural convervation but sequence divergence among other lysine methyltransferases.


SUZ12-VEFS may play a less prominent, but no less important, role in the ordering of the activation loop. It has a backbone interaction with the activation loop and help structuring the activation loop.

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