Allosteric Activation Dictates PRC2 Activity Independent of Its Recruitment to Chromatin (Molecular Cell)

Lee and Yu et al. dissect the stepwise mechanism of PRC2 activation involving the EZH2-SRM and EED anchorage regions. Mutations in these regions diminish PRC2 activity in vivo and override the hyperactivity of oncogenic EZH2 mutations but do not affect PRC2 association with chromatin. ?-Helical mimetics against SRM abrogate PRC2 activation.