Interpreting the CTCF-mediated sequence grammar of genome folding with AkitaV2
Fig 7
CTCF sites do not mediate feature-specific genome folding.
A) Illustration of the test for CTCF feature specialization using two distinct layouts: (i) a ’boundary’ with two divergent sites, 180bp apart, versus (ii) a ’dot’ with two convergent sites, 400kb apart. CTCF insertions are shown as green rectangles (core motifs) with pink flanks (30bp), arrows indicate the orientation of the CTCF site. B) Scatterplot of boundary vs. dot strength (n = 1,500 CTCF sites). Boundary strength is the overall intensity of the map; dot strength is the local average signal within versus around the dot. Six CTCF sites spanning a range of strengths are highlighted with colored dots. C) Predicted maps for boundary and dot scenarios for the six highlighted CTCF sites in panel B. D) Predicted maps for symmetric (<<<>>>) and asymmetric (<<<<<<) insertions for a cassette of six CTCF sites into the middle of a background sequence. E) Insulation scores calculated using sliding diamond windows of three sizes (32.7kb, 131kb, 262.1kb), shown for the central 163,84kb of the map. Note that insulation minima display an offset for the asymmetric case, and the same coloring used for window sizes in E and F. F) Insulation minima offset for indicated CTCF cassette insertions. Insulation offset is the position of the insulation score minima relative to the center of the sequence (window sizes of 32.7kb, 131kb, 262.1kb). Each point represents the average across 100 strong CTCF site insertions. Note the insulation offset increases with the asymmetry of the inserted CTCF site configuration and is more pronounced for larger window sizes. G) Histogram of bins around disruption-sensitive TAD boundaries stratified by their orientation. To obtain bin orientation, we: disrupted sequences in non-overlapping 2048 bp bins around each TAD boundary, took the bin with the highest disruption score, and assigned a left (pink) or right (blue) orientation if all CTCF sites within a bin are aligned in the same orientation. Bins without assigned orientations shown in grey. The black line shows the smoothed total number of disruption-sensitive bins (across all orientations).