Fig. 2: Local and global effect of natural genetic variation on the Kupffer cell epigenome.

a, Scatter plots of log₂ (tag counts) for ATAC-seq signal at the union set of irreproducible discovery rate (IDR) ATAC-seq peaks across all strains; n = 4 per group. b, Scatter plots of log₂ (tag counts) for H3K27ac ChIP–seq signal at the union set of IDR ATAC-seq peaks across all strains; tags are annotated with a window size of 1,000 base pairs (bp) centered on the middle of the IDR peak; n = 3 per group. c, Overlap of active and accessible genomic loci for each strain. Accessible loci are defined as sites with >16 HOMER-normalized ATAC-seq tags. Active loci are defined as sites with >32 HOMER-normalized H3K27ac ChIP–seq tags. d, Strain-specific epigenetic signals associated with transcriptional activation. Cd300e expression and H3K27ac acetylation of nearby enhancers are specific to A/J Kupffer cells. Trem2 is preferentially expressed in BALB/cJ Kupffer cells and is associated with increased acetylation of an intronic enhancer. Irak3 is preferentially expressed in C57BL/6J Kupffer cells and is associated with C57BL/6J-specific ATAC-seq peaks and increased acetylation of nearby enhancers; kb, kilobases. e, Enhancers were categorized into strain similar or strain specific for both ATAC-seq and H3K27ac ChIP–seq data. The table denotes percentages of enhancers at each fold change cutoff that harbor local genetic variation within the 200 bp of the IDR peak. f, Motifs associated with strain-specific active enhancers, defined as loci that had strain-specific increases in H3K27ac. g, MAGGIE motif mutation analysis on strain differentially accessible and active enhancers.