Structural analysis of an active fungal PRC2.

Crystal structure determination of an active polycomb repressive complex 2 (PRC2) from a thermophilic fungus, Chaetomium thermophilum, revealed some long-sought structural mechanisms for assembly, catalysis, and regulation of this important enzyme complex, responsible for trimethylation of histone H3K27 (H3K27me3) and silencing of developmentally regulated genes. In light of the crystal structures of the fungal PRC2 captured in the basal and H3K27me3-stimulated states as well as the structural analysis published previously, (1) we examined surface conservation and electrostatic potential distribution to provide additional insights into functional similarity and divergence between the fungal and human PRC2 and for PRC2 binding by nucleic acids. Structure comparison indicated a conformational change of the catalytic SET domain within PRC2 during transition from the inactive to active state. This conserved structural mechanism is also used by another histone methyltransferase family associated with gene activation for enzyme regulation and may underlie the allosteric stimulation of PRC2 as well.