Fig. 4
K27M alters chromosome accessibility independent of methylation. Integrative analysis of gene expression and chromatin accessibility across SF8628 mutant cells. (A–C) Scatter plot showing the correlation between log2 fold changes in RNA-seq and ATAC-seq data for SF8628 cells with different mutation types (A) SF8628-H3K27M-PRC2WT (B) SF8628-H3K27M-PRC2KO and (C) SF8628-H3K27WT-PRC2KO; each compared to the wild-type. Each point represents an individual gene. The colored lines indicates the linear regression fit, and the R2 value denotes the proportion of variance in ATAC-seq data explained by RNA-seq data. (D–F) Violin plots showing the distribution of median ATAC-seq peak values for genes uniquely dysregulated in each mutation condition: (D) SF8628-H3K27M-PRC2WT, (E) SF8628-H3K27M-PRC2KO, and (F) SF8628-H3K27WT-PRC2KO cells. Downregulated genes are represented in blue, upregulated genes in red, and unchanged genes in green. The white diamond inside the boxplot highlights the median ATAC-seq peak value for each gene category. Statistical significance is indicated by *** (p < 1e-10) and * (p < 1e-3), based on Dunn’s test for multiple comparisons. (G-H) UCSC browser snapshots of ATAC-seq peak values for selected genes including (G) HOX gene clusters, which are upregulated in PRC2 knock outs; and (H) NFIB, HGF, PEX5L, and ABCA8, which are up-regulated in K27M. In each snapshot, K27M, K27WT, K27M-PRC2KO, and WT-PRC2KO are represented in blue, green, red, and orange color respectively