Fig. 4

Short-range chromatin contacts at the ESR1 locus are stronger in tumors. a ChIP-seq genomic tracks for ERα (upper block) and H3K27ac (lower block) in healthy (blue) and tumor (orange) endometrial primary tissues at the ESR1 locus. ESR1 Enhancer 1 and Enhancer 2 are indicated, as well as the mutations found by WGS analyses in metastatic samples. b Representation of the averaged 40-kb resolution Hi-C matrix at the ESR1 locus for the 3 healthy (top) and 3 tumor (middle) tissues or the score difference (bottom) tumor − healthy, where orange indicates higher scores in the tumors while purple higher scores in healthy. The matrices scores are dived by the sum of the matrix. Black lines indicate the topologically associated domains (TADs) identified. c 4C-seq genomic tracks at the ESR1 locus using the ESR1 TSS as view-point (VP) for 2 healthy (top, blue) and 3 tumor (middle, orange) endometrial tissues, and the average difference of score tumor − healthy (bottom). With green arcs are depicted loops detected by H3K27ac HiChIP in Ishikawa endometrial cancer cells. The ribbon around the 4C-seq signal lines indicates the standard error mean (SEM) among biological replicates. d In the top row, observed/expected matrices of sequence-based machine learning prediction in a ±500-kb window surrounding the ESR1 locus. In order from left to right can be found: wild-type sequence, point mutation in a genomic desert (negative control), deletion of the full Enhancer 1 sequence (positive control), introduction of SNVs found by WGS analyses of metastatic endometrial cancer samples. On the bottom row is showed the difference of observed/expected score over the wild-type sequence, where orange indicates higher scores in the altered sequence and purple a higher score in the wild-type one