To illustrate SigProfilerTopography’s capabilities for occupancy analysis, we examined the effect of nucleosome occupancy (measured by MNase-seq data) and binding of CTCF (based on ChIP-seq data), a key regulator of chromatin architecture, on mutational signatures SBS17b and ID2 in the ESCC cohort. The gene discussed is CTCF; the disease is esophageal squamous cell carcinoma.