Fig. 4: Rapid repair of accessible DNA shapes the mutational landscape, but CTCF binding causes extreme local distortions.
a, Nucleosome occupancy shapes the mutational landscape56,57, with higher mutation rates (21 bp sliding window) over the nucleosomes (for example, x = 0), and lower rates in more-accessible linker regions (accessibility measured by ATAC-seq from P15 mouse liver, in purple with scale on the right axis and larger values corresponding to greater accessibility). Mutation and multiallelic rates are shown with shaded 95% bootstrap confidence intervals (also in subsequent panels). b, High rates of multiallelic variation are found at sites of low accessibility and high mutation rate, indicating that high rates of mutation represent slow repair. c, The rate of A→N mutations is the inverse of the overall mutation profile, with high rates of A→N corresponding to accessible regions and rapid repair. d, Mutation rates are dramatically elevated at CTCF-binding sites (21 bp sliding window, in black; single-base resolution, in red). e, High accessibility at CTCF sites again corresponds to low multiallelic variation and low mutation rates (d), with the exception of the mutation hotspot (red arrow), which does not show a corresponding increase in multiallelism, indicating that higher rates of damage cause these hotspots. f, Mutations of A→N closely track DNA accessibility.
