Extended Data Fig. 7: ‘Promoter–enhancer stripe’ links the promoter of PES genes to multiple downstream enhancers.

a, Density plots illustrating the number of enhancers predicted by the ABC model for PES genes versus non-PES genes of GM12878, two-sided Mann–Whitney U test was used. b, Density plots displaying the ABC scores of predicted enhancers for PES genes compared to non-PES genes of GM12878, with statistical analysis conducted using the two-sided Mann–Whitney U test. c, Heatmap visualizing the distribution of ABC model-predicted enhancers associated with PES genes of GM12878. Among PES genes, 66.2% have more downstream enhancers than upstream, 27.1% have more upstream enhancers than downstream, and 6.7% have equal downstream and upstream enhancers. d, Left: APA results between the transcription start sites (TSS) and downstream enhancer loci for PES genes (n = 3,116 E–P pairs); Right: quantification of the pile-up intensity, with the red arrow highlighting the peak at the enhancer site. e, APA result between pairwise enhancers of the same stripy gene (n = 16,614 E–E pairs). All enhancers (marked by H3K27ac) were used. f, Metagene plots showing the signal of PLOR2A and the cohesin subunit SMC3 at PES genes versus non-PES genes in GM12878 cells. g, Similar analyses as in a performed for mESC. h, Pile-up results comparing non-PES genes (n = 600) in untreated, RAD21-depleted, and WAPL-depleted bulk Micro-C data from mESC. i, Metagene plots illustrating the distribution of H3K27ac, POLR2A, SMC1A, and RAD21 at ‘PES genes’ versus non-PES genes in mESC. j, APAs between the TSS and multiple gene body enhancers of PES genes (top, n = 2,260) and non-PES genes (bottom, n = 1,109), plotted for untreated, RAD21-depleted and WAPL-depleted mESC Micro-C. k, APAs between pairwise gene body enhancers of PES genes (top, n = 9,510) and non-PES genes (bottom, n = 3063), plotted for untreated, RAD21-depleted and WAPL-depleted mESC Micro-C. l. Top: scatter plots of loop scores plotted for all E–P interactions between gene body enhancers and promoter of stripy (left) and non-PES genes (right) in the untreated and Rad21-depleted cells. Detected E–P loops were labeled as orange cross, non-loop E-P interactions were labeled as blue dot. The E–P interactions were grouped as strengthened, unchanged and weakened. Bottom: pile-up of loop and non-loop E–P interactions of PES genes for weakened (left) and unchanged (right) interaction upon cohesin depletion.