Supplementary Figure 6: One face of PRC2 clusters binding sites of multiple regulatory factors.

a, Histogram of distances that were measured between cross-linked lysine pairs within the PRC2 core subunits. BS3 XL-MS data was generated using the three PRC2 complexes as indicated in the color key (see Fig. 6a–c for cross-linking sites) and distances were measured between lysine pairs within the high-resolution cryo-EM structure of the PRC2-AEBP2-JARID2 complex (PDB: 6C23). b, Randomized distances histogram was generated after randomly selecting N lysine pairs and measuring the distances between them over the same structure as in (a), where N is the number of observed cross-linked lysine-pairs in each of the datasets used in (a). c, Front (center) and, rear (left) views, and 20 ° rotation with respect to the front view (right), of the PRC2-AEBP2-JARID2 structure presented in Fig. 6d, using the same color code as in Fig. 6. d, The structure as shown in (c), represented in assorted colors according to the four PRC2 core subunits. AEBP2 and JARID2, as well as the regulatory and substrate peptides, are colored according to the same color key as in Fig. 6d. e, RNA-linked peptides that were identified using targeted RBR-ID (RBR-ID score > 5) were mapped to the highresolution structure of PRC2 (PDB: 6C23 and 5WAI). f, RNA-linked peptides that were identified using RBDmap in 2 or 3 replicates are presented on the same structure and views as in (e), for a direct comparison