Supplementary Figure 4: MLL2 catalytic activity contributes to the promoter-focused organization of interactions at bivalent genes.

a, Scatterplot of eigenvectors in Mll2^WT versus Mll2^CD ESCs. b, Pearson linear correlation between the proportion of bivalent genes with respect to the total number of genes in the genome, with the proportion of A-to-B with respect to B-to-A switchers. Red dots represent chromosomes with a ratio (B to A/A to B) higher than 1.0. c, Matrix of normalized differences in correlation coefficients between Mll2^WT and Mll2^CD on chromosome 2. The middle panel shows bins that switched from A to B compartments (green dots) and from B to A compartments (orange dots). Lower panels zoom in on the Hoxd cluster and nearby bins, with ChIP-seq of H3K4me3 and H3K27me3, and the behavior of A/B compartments. The genome is binned in 100-kb bins, and the region covers 73–76 Mb of chromosome 2. d, Top, average log₁₀ value of observed versus expected interaction meta-matrices for the region ±250 kb from the TSS of the indicated genes. Interaction submatrices are corrected for direction of transcription and normalized by decay. The distribution of gene size is shown in gray. Bottom, differential interactions in Mll2^CD as compared to WT. e, As in d for non-bivalent gene subsets. f,g, 3D interaction meta-plots (10-kb resolution) depicting observed versus expected interaction frequencies between the TSS of bivalent genes (f) and non-bivalent genes (g). Hubs visualize intra-TAD (300 kb–1 Mb) crosstalk between TSS. Areas shown are centered on the respective TSS (±150 kb).