Response to Comment on "Structural basis of histone H3K27 trimethylation by an active polycomb repressive complex 2"

Abstract

Zhang et al suggested that in the crystal structure of a polycomb repressive complex 2 from Chaetomium thermophilum (ctPRC2), a flexible linker region, but not the H3K27M cancer mutant peptide, better fits the electron density. Based on our new data, we agree with this alternative interpretation and provide the crystal structure of ctPRC2 bound to a bona fide H3K27M sequence.

Figure 1. Crystal structure of ctPRC2 bound to H3K27M

(A) Residues 532–539 of Suz12(VEFS) are replaced by residues 22–30 of histone H3K27M. Ezh2 and Suz12(VEFS) are indicated by grey boxes. (B) The Fo−Fc omit (left) and 2Fo−Fc (right) electron density maps contoured at 2.0σ and 1.0σ respectively that correspond to H3K27M and SAM are indicated by the green and blue meshes. Structural models are shown in sticks. The side chain of the mutated methionine residue in H3K27M is clearly defined to occupy the lysine access channel and contact SAM.