a, Tissue specificity of the usages of promoters (H3K4me3 and polII), enhancers (H3K4me1) and CTCF-binding sites. b, Distribution of the Spearman correlation coefficient of H3K4me1 at enhancers and polII at promoters of random permutation, the nearest TSS model, and the CTCF block model. c, Enhancers and promoters form co-regulated clusters of different sizes, as shown by the Spearman correlation coefficient of H3K4me1 at enhancers and polII at promoters on chromosome 19. d, Hi-C interaction heatmap showing that the physical partitioning of the genome is highly correlated with the EPUs that encompass Pcdhα, Pcdhβ and Pcdhγ gene clusters on chromosome 18. Top: normalized Hi-C interaction frequencies in mouse cortex as a two-dimensional heatmap. Bottom: UCSC genome browser views of the same regions, including the identified EPUs and the ChIP-Seq data (H3K27ac, H3K4me1, H3K4me3, polII and CTCF) in cortex. e, The average normalized Hi-C interaction frequencies for enhancer–promoter pairs within EPUs, between EPUs, and expected by random chance.