Fig. 2

Characterization of SEM^PINORES by RNA-, ATAC-, and ChIP-sequencing. A. Heatmap showing ChIP-seq reads of KMT2A, AFF1, H3K79me2, and ATAC-seq reads at all KMT2A::AFF1 binding sites in SEM cells as well as SEM^PINO_RES at the same location, ranked by peak width. Scale bar represents normalized read count. B. Pie chart showing the number of genes for which the expression was significantly (i.e., at false discovery rate (FDR) adjusted p-values of < 0.05) downregulated (blue), upregulated (red), or remain unchanged (gray) between SEM^PINO_RES in comparison to SEM (RNA-seq data; n = 4 biological replicates/sample). C. Venn diagram showing the overlap of downregulated (blue) or upregulated (red) putative KMT2A-fusions target genes (n = 181) (white) in SEM^PINO_RES compared to SEM. The putative KMT2A fusion target genes in this figure comprise the combination of genes identified by four independent studies [9, 20, 24, 25], and D. similar Venn diagrams are presented using the KMT2A fusion target genes from each individual study. E. Forest plot showing hallmark gene sets that were positively or negatively enriched in Geneset Enrichment Analysis (GSEA), based on the Normalized Enrichment Score (NES). F. Heatmap showing the most positively enriched and significantly upregulated genes (n = 50) as well as the most negatively enriched and significsntly downregulated genes (n = 50) in SEM^PINO_RES as determined by GSEA. Data shown represents normalized RNA-seq counts in SEM and SEM^PINO_RES cells cultured for 7 days in either the absence (-) or presence (+) of 50 µM pinometostat of n = 4 biological replicates