Extended Data Fig. 8: Structural organization of the interface between WDR5, MLL1 and RBBP5 subunits.

a, Detailed view of the interface between WDR5, MLL1^SET and RBBP5^AS. The key residues of RBBP5^AS are shown in stick representation with electron microscopy densities. b, Structural comparison of human MLL1 complex with a group of SET-domain histone methyltransferases—including PRC2 (PDB 5KJH), NSD1 (PDB 3OOI) and DIM5 (PDB 1PEG)—shows that MLL1^AS and RBBP5^AS correspond to the activation segment motifs (coloured in blue) of these methyltransferases. c, The input of the HMT reactions related to Fig. 4e. The input amounts of the wild-type and mutant MLL1 complexes were quantified according to the band intensities of MLL1. d, End-point HMT assays of mutant MLL1 complex that carries a deletion of MLL1^AS (residues 3775–3786). Top, the input of the HMT reactions. The input amounts of the wild-type and mutant MLL1 complexes were quantified according to the band intensities of MLL1. Bottom, end-point HMT assays of the wild-type and mutant MLL1 complexes on unmodified nucleosomes. Each assay was repeated at least three times with similar results. n = 3 independent experiments. Data are mean ± s.d. e, End-point HMT assays of mutant MLL1 complex with a deletion of RBBP5^AS (residues 329–336). Top, the input of the HMT reactions. The input amounts of the wild-type and mutant MLL1 complexes were quantified according to the band intensities of MLL1. Bottom, end-point HMT assays of the wild-type and mutant MLL1 complexes on unmodified nucleosomes. Each assay was repeated at least three times with similar results. n = 3 independent experiments. Data are mean ± s.d.