Figure 7.

Loss of Klf5 in intestinal stem cells leads to depletion of H3K27ac at genomic loci. (A) Genome-wide differential H3K27ac analysis²⁷ reveals up- and downregulated regions in Lgr5^ΔKlf5. Volcano plot shows all regions achieving P < .01 with fold-change (FC) depicted by shades of gray (light gray FC <1.7, dark gray FC ≥1.7); red dots mark promoters. Representative IGV tracks for H3K27ac²⁸ and ATAC-seq (blue) at Sfrp5 in Lgr5^Ctrl and Lgr5^ΔKlf5 or Lgr5^Ctrl ISCs, respectively. The shaded boxes mark regions of H3K27ac loss at promoter and putative enhancers. (B) Scatter plots show correlation between duplicate Lgr5^Ctrl or Lgr5^ΔKlf5 H3K27ac ChIP-seq samples. r is the Pearson correlation coefficient. (C) Heatmaps represent ATAC-seq (in Lgr5^Ctrl ISCs; GSE83394) and H3K27ac at 1030 down and 346 upregulated enhancers in Lgr5^ΔKlf5 compared with control ISCs (FC ≥1.7, P < .01). H3K27ac at 256 and 16 down and upregulated promoters, respectively, in Lgr5^ΔKlf5 is depicted to the right. Aggregate plots show average signal intensities at enhancers (left) and promoters depleted for H3K27ac in Lgr5^ΔKlf5. (D) Representative IGV tracks for H3K27ac ChIP-seq,²⁸ ATAC-seq (blue), and RNA-seq (purple) at Prelp and St6galnac1 loci. The shaded regions depict loss of H3K27ac at promoters or enhancers.