Extended Data Fig. 6: Global alteration in H3K27ac, H3K27me3, and H3K27M-modified chromatin in DIPG subtype cells treated with BMP4.

(a) Pie charts show the percentage of genomic distribution of SMAD1 ChIP–seq peaks in the vehicle or BMP4 (50 ng/mL) treated TT150630 cells. The hg38 reference genome distribution was set up for control. (b) Metagene plots showing the average ChIP–seq signal for SMAD1, H3K27ac, H3K27me3 and H3K27M for all of the BMP4 up- (top) and downregulated (down) genes in TT150630 cells treated with vehicle or BMP4 for 2 hr. (c) Identification of subgroup-specific genes with concordant changes in both expression and SEs in TT150630 DIPG cells. x axis: LFC of gene expression between vehicle and BMP4 treatment for 2 hr in TT150630 DIPG cells. y axis: LFC of SEs associated with the gene. Red: significantly upregulated genes. Blue: significantly downregulated genes. Gray: no significant changes in expression. (d) The HOXA family genes heatmap from RNA-seq transcriptome analysis of TT150630 cells treated with BMP4 at the indicated timepoints (n = 2 independent experiments). (e) IGV tracks for H3K27me3 ChIP–seq (with vehicle or BMP4 treated for 24 hr or CHRDL1 KD) in TT150630 cells at indicated genes loci. (f) Identification of subgroup-specific genes with concordant changes in both expression and H3K27ac signals in TT150630 cells. X axis: LFC of gene expression between control (n = 2 independent experiments) and BMP4 treatment (n = 2 independent experiments). Y axis: LFC of H3K27ac signals at a promoter or enhancer associated with the gene. Genes with significantly differentially acetylated regulatory regions between control and BMP4 treatment are shown. Red: significantly upregulated genes. Blue: significantly downregulated genes. Gray: no significant changes in expression. (g) Super enhancers (SEs) detected in TT150630 DIPG CHRDL1 KD cells.