Fig. 4

Activation of de novo enhancers drives oncogenic pathways. a On the left, heatmap showing the ranked differential expression profile of genes associated to M2 de novo enhancers in M2 vs. IMEC-MYC. On the right, correlation plot between the fold change (FC) expression and differential MYC binding in M2 vs. IMEC-MYC, on enhancers of induced genes in mammospheres. Each dot represents a bin of ten genes. b GO of genes associated to M2 de novo enhancers and transcriptionally induced in M2 vs IMEC-MYC. c Heatmap showing the dynamic behavior of MYC and H3K27ac normalized ChIP-seq signals overidentified enhancer regions whose associated genes are transcriptionally induced in M2 with respect to IMEC-MYC with either increased MYC binding in M2 or not. Expression of associated genes is reported. Relevant genes belonging to the two groups are indicated on the right. RPM reads per million. d Notched boxplot showing the distribution of the fold change (FC) of the expression values between M2 spheres and IMEC-MYC of genes associated to de novo enhancers differentially bound by MYC. Horizontal black lines indicate medians. Boxes extend from the first to third quartile and the Tukey method was used to plot whiskers. (*P < 0.05; Student’s t-test). e Tag density plots of H3K4me1, H3K27ac, and MYC normalized ChIP-seq signals in IMEC WT, IMEC-MYC, and M2, centered on enhancers regions associated to genes which are either only transcriptionally induced (left) or also enriched for MYC binding (right) in M2 with respect to IMEC-MYC. f Tables depicting transcription factors binding motifs enrichment at the center (±2 kb) of enhancers associated to genes which are either only transcriptionally induced (left) or also enriched for MYC binding (right) in M2 with respect to IMEC-MYC