Fig. 3

Enhancer RNAs and differential epigenetic macrophage landscape. a Schematic defining distal regulatory DNAs by epigenetic signatures and proximity to expressed gene (maximum TPM ≥ 1 across samples) bodies in MDMs. b Outline of context-specific eRNA analysis procedure. c A bar plot showing the percentage of distal enhancers (orange) and distal ATAC-only regions (brown) that contain expressed eRNAs (CPM ≥1). p value was calculated by two-tailed fisher test. ***p < 0.001. d Correlation of log2 fold change of eRNAs and ATAC regions (upper) or H3K27ac peaks (lower) in HD vs. UT. Pearson’s r and p values are shown. e Volcano plot showing differentially expressed eRNAs following acute LPS stimulation. The nearest gene for the top three hits are highlighted. f Example of differential eRNAs proximal to differentially expressed genes (TMPRSS13 and IL10RA) for acute LPS response and tolerance. The average sequencing depth for RNA and epigenetic marks are shown on the y axis. Regions with differential eRNAs, ATACs and H3K27ac are highlighted in grey. g mRNA expression of each gene indicated in f was compared upon LPS response (HD vs. UT) and LPS tolerance (LDHD vs. HD) with samples from 6 different donors (indicated by different colour dots with linked lines). p value was calculated by linear regression. ***p < 0.001