Fig. 2

Transcription factor motifs, context-specific eQTLs and differential chromatin accessibility and modifications. a Heatmap showing the enrichment of transcription factor (TF) binding motifs in differential ATAC versus non-differential ATAC regions. Greyscale values indicate enrichment levels. Only statistically significant results (FDR < 0.05) are shown. The LPS treatment conditions are shown on the x-axis and enriched TF motif clusters on the y-axis. Motifs enriched in both upregulated ATAC regions upon LPS response and downregulated ATAC regions upon tolerance are highlighted on the right panel. b Example of proinflammatory cytokine and chemokine genes TNF (left panel) and CXCL11 (right panel), for which the promoter regions have differential ATAC regions containing NFkB motifs. The average sequencing depth (normalized per million mapped reads) for RNA-seq and ATAC-seq from 6 independent biological replicates are shown on the y axis. c Heatmap showing the log2 fold change of gene expression (upper: HD vs. UT; lower: LDHD vs. HD) for the enriched TFs. Gene upregulation is indicated in brown and downregulation in green. d Forest plot showing enrichment of differentially expressed genes linking differential ATACs compared to non-differential ATACs using MDM eQTLs (upper), iPSM eQTLs (middle) or monocytes eQTLs (lower). The odds ratio and p-values are depicted and were calculated using a two-tailed Fisher test. In case multiple genes were attributed to an ATAC peak, the gene associated with the most significant eQTL that overlaps the peak was selected for the analysis. e KLF4 locus showing differential chromatin accessibility and H3K27ac (region highlighted in grey) harbouring context-specific KLF4 eQTLs (red circles). See also Fig. S2