Fig. 5: Epigenetic conservation at cCREs is correlated with conservation in expression of their putative target genes.

a, The percentage of peaks predicted to be enhancers (ABC score ≥ 0.02) with mappability-normalized chromatin accessibility. P values were calculated using χ² tests. b, The mappability-normalized H3K27ac log₂-transformed CPM within ±2 kb of cCRE centres for the specified groups. P values were calculated using two-sided unpaired Wilcoxon rank-sum tests. Sample sizes are reported in Supplementary Table 34. c, Density plots for gene expression conservation index values from each indicated comparison. Target genes are categorized as either human-biased distal cCRE targets or mammal level 3 distal cCRE targets. P values were calculated using two-sided unpaired Wilcoxon rank-sum tests. d, Box plots of ABC putative target genes for each distal cCRE from the indicated conservation group. P values were calculated using two-sided unpaired Wilcoxon rank-sum tests. Sample sizes are reported in Supplementary Table 34. e, The conservation levels of human TAD boundaries, including human-specific, level 0 (sequence conserved), level 1 (tissue conserved) and level 2 (cell type conserved), across mammals. f, The conservation levels of genes and cCREs in the indicated conservation groups. g, Heat maps for pairs of human-biased cCREs targeting human-biased genes in the same cell type. The values represent the smallest −log₁₀-transformed false-discovery rate (FDR) for any comparison between human and another species. Rows are scaled to visualize relative differences across cell types. h, WashU browser snapshots of FOXP2 (left) and RYR3 (right) showing chromatin accessibility, H3K27ac and RNA signals in human and chromatin accessibility and RNA for macaque, marmoset and mouse for MGC (left) or ASC (right) and L6 CT. The tracks display concordance of genome alignment from human (hg38) to the indicated species. For the box plots in b, d and f, the centre line represents the median, the box limits encompass the 25th to 75th percentiles and the whiskers represent 1.5× the interquartile range.