Extended Data Fig. 9: Response of WT and K27M mutant NSCs to EZH2 inhibition.

a. Cellular viability dose-response in PP5W (black) or PP5K (red) cultures treated with the indicated small-molecules. Mean ± s.d., n = 3 independent samples. b. GO analysis of genes significantly upregulated (top panels) or downregulated (bottom panels) in PP5W and PP5K cultures following treatment with Tazemetostat. c. RNA-seq volcano plots showing expression changes in H3.3-K27M mutant mouse NSC cells treated with Tazemetostat (left) or a DMG cell line following shRNA SUZ12 knockdown (right). Total numbers of up/down regulated genes are indicated, as are the numbers of up/down regulated genes gaining SUZ12 at their promoters in H3.3-K27M human NSCs. In mouse cells, the homologs of genes gaining SUZ12 are highlighted. d. Plots showing log₂ fold-change in expression for the set of non-PRC2 repressed loci in Tazemetostat treated PP5W or PP5K cultures, n = 3 independent samples. Presented are median values and interquartile ranges (IQR), with whiskers representing quartiles 1/3 ± (1.5 × IQR) respectively. e. Genomic tracks showing RNA-seq data at the INK4A-ARF locus (chr9:21,961,091-22,001,052) in PP5W and PP5K cultures treated with DMSO or Tazemetostat. Indicated are the INK4A and ARF specific exons for each transcript. f. Plots showing log₂ expression values for the indicated genes in H3.3 WT or K27M NSCs (left panels), n = 4 independent samples or PP5K cells treated with DMSO or Tazemetostat (right panels), n = 3 independent samples. Presented are median values and interquartile ranges (IQR), with whiskers representing quartiles 1/3 ± (1.5 × IQR) respectively. g. Plots presenting the log₂ fold-change in gene expression for the set of neurodevelopmental regulatory genes which lose H3K27ac and chromatin accessibility at their promoters in Tazemetostat treated PP5W or PP5K cultures, n = 3 independent samples. Presented are median values and interquartile ranges (IQR), with whiskers representing quartiles 1/3 ± (1.5 × IQR) respectively.