Fig. 3. β-cell circadian cistrome is determined by tissue-specific enhancer repertoire.

(A) Overlap of genes identified at BMAL1 binding sites in β-cells and liver (top). Scatter plots show BMAL1 binding in liver (y-axis) versus β-cells (x-axis) within 500bp windows surrounding peaks identified in each tissue (middle). Browser track view of BMAL1 binding in β-cells and liver at the Gpr137 locus (bottom). (B) Overlap of cycling and direct BMAL1 target genes in β-cells that have been reported to cycle in liver (top). Cycling BMAL1 direct target genes containing shared or unique binding sites in β-cells and liver (bottom). (C) Heatmaps comparing binding of indicated factors within 1kb windows surrounding promoter (3,492) and enhancer (5,771) localized H3K4Me2 peaks annotating to genes containing cycling RNAs in WT islets. Histograms summarizing normalized tag counts for H3K27Ac (in β-cells and liver) and PDX1 (in β-cells) across 6kb span centered at all β-cell H3K4Me2 peaks (bottom). (D) Box and whiskers plots (whiskers represent IQR 1.5) comparing BMAL1 binding in β-cells and liver at loci corresponding to H3K4Me2 peaks defined in heatmaps. Poised enhancers refer to H3K4Me2 sites that do not co-localize with H3K27Ac, whereas active enhancers are defined as H3K4Me2 sites co-localized with H3K27Ac. ***p<0.0001 by Mann-Whitney non-parametric, unpaired t-test. All reported ChIP-seq tag counts normalized per 10⁷ reads.