Fig. 4

Super-enhancers in unstimulated and activated macrophages. a A scatterplot of P300 density at enhancer sites in resting versus stimulated macrophages. b The density of P300 at many enhancers and SEs is dynamically changed upon stimulation of macrophages. ChIP-seq data are from [36]. Analysis of top 25 most highly induced SEs upon macrophage activation (top) or repressed SEs (bottom). Density of P300 in activated macrophages is shown compared to resting macrophages. For those SEs located within 100 kb of a macrophage inducible gene, the name of the gene(s) is shown along with the fold change in expression (Top: increase in fold change, bottom: decrease in fold change). The absence of a gene name denotes the absence of an annotated protein-coding gene within 100 kb of the SE. RNA-seq data are from [34]. *continued from figure due to lack of space: Fam63a (4.38x), Golph3l (2.19x), Lysmd1 (4.92x), Prune (5.89x), Scnm1 (2.13x), Vps45 (2.46x), Tmod4 (4.26x). c The expression of many genes from (B) is blocked when TLR4-stimulated macrophages are treated with iBET. GRO-seq data are from [35]. d A SE near Pim1 is induced following TLR4 stimulation. GRO-seq reveals that this SE is also transcribed when active. e (Top) Shown is a local association plot for a cis-eQTL that regulates the SGK1 gene. The most significantly associated SNP from the linkage disequilibrium (LD) region is rs1281791. Dotted line designates the R-squared value of 0.8 used as a cutoff for determining linked SNPs. Blue line indicates genomic recombination rate (y-axis on right). The entire LD region is also located within a SE active in human CD14⁺ monocytes. eQTL data are from naïve CD14⁺ cells [49]. (Bottom) Expression of SGK1 in human CD14⁺ monocytes, along with H3K27ac density (data from GSE18927). f Enrichment of human monocyte eQTLs in SEs vs. CEs. 550/1019 monocyte SEs overlapped a naïve monocyte eQTL LD region (54 %), compared to only 5471/19028 CEs (29 %). eQTL data are from [49]