Fig. 6: Synthetic ecteinascidins bind to CpG-rich sequences located in open chromatin regions.

a Venn diagram of drug-binding sites (Bio-lurbi in the left and Bio-PM54 in the right) in 501mel vs. MM029 cells (n = 3). b Pie chart showing the distribution of annotated peaks (in percentages) for Bio-lurbi (top) and Bio-PM54 (bottom) all over the genome (hg19) in 501mel cells (n = 3). c Left panel: Venn diagram (n = 3) between promoters bound by Bio-lurbi or Bio-PM54 and genes down-regulated by lurbinectedin or PM54 in 501mel cells. Right panel: the two Venn diagrams (n = 3) were merged. Representation factor and hypergeometric p-value are indicated and were determined using Graeber lab software. Hypergeometric distribution test was used to determine the p-values. d Upper panel: Metaplot distribution (n = 3) of Bio-lurbi, Bio-PM54, BRD4, RNAPII, H3K27ac, H3K27me3 enrichment and ATAC-Seq signals in a ± 5 kb window around the occupied DNA binding sites of Bio-lurbi in differentiated 501mel cells. Lower panel: Heatmap profiles representing the read density clusterings obtained with seqMINER for the DNA-occupied sites of Bio-lurbi in differentiated 501mel cells relative to Bio-PM54, BRD4, RNAPII, H3K27ac, H3K27me3 enrichments and ATAC-Seq signals. Peak order is determined by Bio-lurbi and identical for all clusterings. e Venn diagram (n = 3) between Bio-lurbi (left) or Bio-PM54 (right) binding sites and positive ATAC-seq peaks (indicative of chromatin open regions) in differentiated 501mel cells. f Venn diagram (n = 3) between Bio-lurbi (left) or Bio-PM54 (right) binding sites and human CpG islands in differentiated 501mel cells. g Venn diagram (n = 3) between Bio-lurbi (left) and Bio-PM54 (right) binding sites in differentiated 501mel cells and human CpG islands. Human CpG islands are divided into those found in open chromatin regions (CpG islands/ATAC(+)) and those found in closed chromatin regions (CpG islands/ATAC(−)).