Fig. 3: Gene expression profiles of NOTCH1^ΔPEST transduced CLL cells.

a Heatmap DE genes following NOTCH1^ΔPEST overexpression in CLL cells (n = 13). Libraries were generated from mRNA isolated from FACS sorted GFP⁺ cells 4 days post infection. b Gene ontology (GO) and Gene set enrichment analysis (GSEA) results of NOTCH1^ΔPEST DE genes identified by RNAseq. Upregulated (left) and downregulated (right) gene-sets are indicated by bars. Normalized Enrichment Scores are shown on the left black Y-axis, FDR q values on the right Y-axis. c DE genes identified by RNAseq were validated on a cohort of NOTCH1-mutated patients with del13q (left panel) or trisomy 12 (right panel). d Scatter plot showing the Log2FC mean of DE genes in tri12 (n = 7, light gray dots, x-axis) vs del13q (n = 6, black dots y-axis) following NOTCH1^ΔPEST overexpression. Red dots represent commonly DE genes between the two different groups. Error bands indicate the 95% percentile of the mean. e Unsupervised principal component analysis of the H3K27ac ChIP-seq profiles of n = 5 paired CLL primary cases transfected with empty vector (EV) or NOTCH1^ΔPEST (N1^ΔPEST). 43,300 independent genomic regions were analyzed to generate the PCAs. f Heatmap shows VST normalized H3K27ac signals for those peaks identified in principal component 5, associated with promoters or gene bodies (n = 422 peaks). g Example targeting HES1 gene, identified to have an increase H3K27ac signal in NOTCH1^ΔPest expressing samples. The mean value of the subtracted signal calculated for each individual paired sample per 1 bp is shown. One representative analysis out of 5 is shown.