Fig. 1
Measuring co-localization of TF sites in Hi-C contact maps and genome structures. a A schematic overview of using Hi-C contact data to quantify the spatial co-localization of TF binding sites, both within the same type and between different types. A section of a Hi-C contact map for human chromosome 9 at 5 kb resolution (upper right triangle) showing normalized contact counts of lymphoblastoid GM12878 cells [24] and the corresponding count expectation, given sequence separation (lower left). The illustrated color scale corresponds to the binned contact counts. Illustrative binding sites for two TFs (YY1:blue and NRF1:green), identified by a combination of ChIP-seq and sequence motif scans, are shown as dashed lines. Paired contact possibilities between these sites are shown on the Hi-C map at the intersections of these lines, and the corresponding observed and expected count values for each pair are extracted into separate columns (mid-right panel). For each TF:TF site pair, the log2(Observed/Expected) score is shown in the last column (right); it is the summation of these values that is used to calculate the CCL-scores for either a single TF (homotypic) of between different TFs (heterotypic). b Studying TF sites in a 3D genome structure calculated from single-cell Hi-C. A genome structure for a single cell, calculated using single-cell Hi-C, provides relative three-dimensional coordinate positions for all chromosomes, here modelled as 100-kb particles. The complete genome is shown as thin sections through the center of five aligned coordinate models and colored according to chromosome identity (bottom). The locations of TF binding sites within these structures can be identified (top). Here, β-catenin sites are shown in red and Tcf3 sites in blue. The data is shown for mouse ESC “Cell1” as published in Stevens et al. [36]. c Identifying co-localized TF sites in a genome structure. An enlarged section of one structure model shown in b shows the modelled chromatin backbone path (grey/yellow) and illustrates how TF sites within a specified radius of a query point (center of dashed circle) can be identified. The solid spheres represent the restrained points in the middle of 100-kb chromosome regions (so there is also 100 kb between points). The repulsive radius (r) used in the structure calculation, to separate the restrained points in 3D space, corresponds to half of the ideal sequential point separation (equivalent to 50 kb). The points that are close in sequence to the query (within 300 kb, either side), which are excluded from its analysis, are shown in yellow