Fig. 3

Hypomethylated aDMRs are enriched at intragenic enhancers in highly expressed liver-specific genes. a Clustered feature interaction maps of spatial overlap between hypomethylated aDMRs (columns) and a selection of genomic, histone and transcription factor features (rows), showing WT (WT; left) and dwarf (D; centre left) aDMRs. Red indicates an overlap between an aDMR and a feature and blue no overlap. Interaction map x-axes are scaled by number of aDMRs. The percentage overlap (centre right) and fold enrichment observed/expected (random) overlap (right; units of fold) for each feature are given. b The overlap between enhancers that contain hypomethylated aDMRs in WT and Ames dwarf mice. Enrichment of overlap observed/expected 153-fold, p < 0.001. c Mean percentage methylation per replicate across enhancers that contain hypomethylated aDMRs in both WT and dwarf mice. For 2-month-old WT (WTY; light blue), 22-month-old WT (WTO; dark blue), 2-month-old dwarf (DY; light red) and 22-month-old dwarf (DO; dark red) mice. WTY versus WTO, DY versus DO, WTO versus DO all p < 0.001 (indicated with double asterisks) and WTY versus DY p < 0.05 (indicated with a single asterisk) (two tailed t-test on arcsine transformed proportions). d Kernel smoothed line plots of selected enhancers overlapping hypomethylated aDMRs, ±5 kb. Replicates for WTY, DY, WTO and DO are represented by solid blue, solid red, dashed blue and dashed red lines, respectively. DMRs are highlighted in pink and CpGs in black. H3K4me1 and H3K27ac enrichment (ChIP-seq) is indicated. e The percentage methylation across all enhancers containing hypomethylated aDMRs unique to WT mice (6193 regions from Fig. 3b). Replicate samples (four mouse livers) are in columns and the aDMRs in rows. The intensity of the heatmap represents row scaled percentage methylation (Z-score), with values ranging from lower to higher methylation shown as blue to red. f Mean number of enhancer overlapping hypomethylated aDMRs per gene for WT (blue) and Ames dwarf (red) mice. Genes are split into quartiles by expression (Q1 = highest, Q4 = lowest). Unexpressed genes (FPKM = 0) are given (U). g Observed and expected overlap (in base pairs) of hypomethylated DMRs (WT, WT only; dwarf, dwarf only; shared, shared between WT and dwarf) with super-enhancers; **P < 0.01