Supplementary Figure 1 : Expanding cCRE anchors to include transcription factor binding sites

Supplementary Figure 1 | Expanding cCRE anchors to include transcription factor binding sites

a, Histogram depicting the percentage of transcription factor (TF) peaks overlapping rDHSs. TFs with less than 90% overlap constituted a distinct set of TFs (depicted in the word cloud) such as MAFK, CEBPB, and ZNF274. Size of TF name is proportional to the number of TF experiments with less than 90% overlap. Full results can be found in Supplementary Table 2e. b, Heatmap depicting the overlap coefficient between TF peaks, which do not overlap rDHSs, between experiments with low rDHS overlap as defined in the dashed box in a. Five primary TF experiment clusters were defined using hierarchical clustering. c, Density plots depicting the average 100-way vertebrate alignment PhastCons conservation score for rDHSs (green) and proposed TF rCluster anchors (purple). Three sub-categories of TF rClusters, as defined in b, are shown including CEBPB sites (blue), ATF/CREB1 sites (orange), and MAFK/MAFF sites (teal). Non-cCRE regions are shown in white. All groups were significantly more conserved than non-cCRE regions (pairwise, two-sided Wilcoxon rank sum test with FDR correction, p < 4.6 × 10−16), supporting their inclusion in the Registry of cCREs. d, Example of rDHS (green) and TF rCluster (purple). The rDHS has high chromatin accessibility in K562 and HepG2 as measured by DNase-seq and ATAC-seq data. The TF rCluster has low chromatin accessibility. Both sites overlap TF ChIP-se1 peaks with the TF rCluster overlapping peaks for MAFK, MAFF, ZNF316, and C11orf30. e, Line plot depicting the number TF rClusters we identify stratified by the number of transcription factors supporting that cluster. Arrow denotes our threshold ≥ 5. f, Boxplots depicting average PhastCons 100-way vertebrate conservation for TF rClusters stratified by (1) number of supporting transcription factors (x-axis) and (2) overlap with rDHSs (green for overlapping, purple for non-overlapping). e, Line plot depicting the percent of TF rClusters in the great-ape specific group as defined by Zoonomia conservation stratified by the number of transcription factors supporting that cluster. Arrow denotes our threshold ≥ 5.