Fig. 4

Hypermethylated aDMRs are enriched at bivalent CpG islands. a Clustered feature interaction maps of spatial overlap between hypermethylated 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 is given. b Percentage of WT and Ames dwarf mice aDMRs that overlap with either histone modifications or a panel of 30 transcription factors (Histone or TF; blue) or neither (Neither; red). c The base pair (in mega-base pairs) overlap between hypermethylated aDMR-containing CpG islands and hypermethylated aDMR-containing bivalent regions in WT mice. Enrichment of overlap observed/expected 1302-fold, p < 0.001. d Kernel smoothed line plots of selected bivalent CpG island (CpGI) overlapping hypermethylated aDMRs, ±5 kb. Replicates for 2-month-old WT (WT Young) and 22-month-old WT (WT Old) mice are represented by solid blue and dashed blue lines, respectively. DMRs are highlighted in pink and CpGs in black. H3K4me3 and H3K27me3 enrichment (ChIP-seq) is indicated. e Liver bivalent regions that contain hypermethylated aDMRs in WT and dwarf mice. Enrichment of overlap observed/expected 173-fold, p < 0.001. f Mean number of hypermethylated bivalent 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)