Fig. 2

Frequently mutated ERBS are associated with more chromatin loops and higher gene expression. Boxplots presented in this figure illustrate the lower quartile (Q1) and higher quartile (Q3) as the box, median as the line inside the box, and 1.5 × interquartile range (IQR = Q3 - Q1) as the whiskers. a Boxplot depicts corrected long-range chromatin contact frequency from Pol2 ChIA-PET data in MCF-7 cells, for ERBS with different numbers of somatic mutations in BRCA-EU. The contact frequency was corrected using a negative binomial linear regression model to remove the effect of ER binding intensity (Additional file 1: Figure S5). Gray dash line indicates the average corrected contact frequency for all ERBS. b Boxplot represents expression levels of genes that are topologically associated (within the same TAD and associated with ERBS via ChIA-PET loop) or linearly associated (50 kb distance) with ERBS. ERBS were grouped according to the number of mutations within 200 bps of its summit (same as in panel a). c Mean number of somatic mutations is plotted for ERBS that are associated with good outcome, poor outcome/metastasis and shared by at least 75% of breast cancer patients (core ERBS) [23]. The average mutation number was calculated based on random sampling of 100 ERBS from each group for 50 times. P values are calculated using two-sided Student’s t test. d Bar plot shows the number of BRCA-EU patients carrying mutations at the ERBS, which contained the most number of somatic mutations within 200 bps of the summit (except for FOXA1, somatic mutations ~ 100 bps beyond the 200-bp limit were included due to its recurrence) across all the patients. Asterisk indicates if there are recurrent mutations (existing in at least two BRCA-EU patients). Gene symbols for the ERBS within coding regions are shown inside the bars. The two ERBS that are characterized in this study are in bold font