Extended Data Fig. 6: Increased genome-wide, DSB-induced, cohesin binding is enhanced within damaged TADs.
From: Loop extrusion as a mechanism for formation of DNA damage repair foci
a, Top, contact matrix (5-kb resolution) showing log2[observed/expected] before or after DSB induction on a region showing a loop on chromosome 20 and devoid of AsiSI site (no DSB). Loops anchors are circled and indicated by red and blue bars. Bottom, genome browser screenshot showing the SCC1-calibrated ChIP–seq on the same region before and after DSB induction. Cohesin enrichment at the loop anchors (blue and red bars) is increased after DSB (black arrows) compared to before DSB (grey arrows), in agreement with increased loop strength (grey and black circles, top). b, Violin plots showing SCC1 enrichment at cohesin peaks (n = 46,194) before and after DSB induction. Paired one-sided Wilcoxon test. c, Genomic tracks of γH2AX (red) and SCC1 ChIP–seq signal before (blue) and after (purple) DSB induction. The ratio between before and after DSB induction (grey) is also shown (log2[+DSB/−DSB]; 10-kb smoothed). d, Quantification of SCC1 recruitment on loop anchors at different distances from DSB sites as indicated (from left to right, n = 1,610, 3,161, 1,930, 3,232, 4,786, 25,263, 114,461). Centre line, median; box limits, first and third quartiles; whiskers, maximum and minimum; points, outliers. e, γH2AX ChIP–seq signal and Hi-C signal at different distances from a damaged TAD on chromosome 1 before (−DSB) and after DSB induction (+DSB). Green circles, chromatin loops. f, APA plot on a 200-kb window (10-kb resolution) before (−DSB) and after DSB induction (+DSB) calculated for all loop anchors, in damaged and undamaged TADs. The fold change between the signal (central pixel) and the background (lower left corner 5 × 5 pixels) is indicated. g, Differential loop strengths in undamaged or damaged TADs (Methods), computed from Hi-C data obtained before and after DSB, from replicates 1 and 2. P values between before and after DSB are indicated (Wilcoxon test, μ = 0). The increased loop strength following DSB is significantly higher in damaged TADs than in undamaged TADs (paired two-sided Wilcoxon test) in both Hi-C replicate experiments. Replicate 1: undamaged, n = 2,936; damaged, n = 264. Replicate 2: undamaged, n = 3,181; damaged, n = 302. Box plots as in d.
