Fig. 2: Methylomic and chromatin accessibility signatures of aging in the dorsal hippocampus.

a Violin plots showing the distribution of EM-seq methylation measurements of CpG sites across groups. Plots are based on a 1 M sample of CpGs. b, c Bar plots describing the proportion of hyper- and hypomethylated aging-DMRs mapped to CpG island (b) or gene (c) locations, as compared to the distribution of all of the profiled CpG sites. d Genomic plots showing the DNA methylation profiling values in young and old subjects of two regions containing aging-DMRs (grey boxes) associated with the Cbln1 and Pink1 genes. Below, the tracks indicate the presence of gene exons, CpG islands and ENCODE murine forebrain P0 enhancer Pp elements. On the right of the plots, the boxplots indicate the RNA-seq expression measurements (VST units) for the Cbln1 and Pink1 genes across young and old subjects (n = 6 for all groups; p adj <0.05 for two-sided Wald tests across all data). All box plots shown indicate median value, interquartile range (IQR), up to 1.5 IQR (whiskers), and individual data points showing minimum and maximum value. e, f Bar plots describing the proportion of up- and down- aging-DARs mapped to CpG islands (e) or gene (f) locations, as compared to the distribution of the consensus peak set (“All”) or the whole genome (“Gen”, 200 bp bins). g Heatmaps showing the significant (FDR < 0.05, one-sided Fisher’s exact tests) LOLA enrichments in log2(odds ratio) of chromatin states associated with aging-DARs, either up-DARs defined with FDR < 0.05 (two-sided Wald tests) or up- and down-DARs defined with unadjusted p < 0.05 (two-sided Wald tests). The code for the ENCODE chromatin states shown is: Promoter, Active (Pr-A), Weak (Pr-W), Bivalent (Pr-B) and Flanking (Pr-F); Transcription, Strong (Tr-S), Permissive (Tr-P) and Initiation (Tr-I); Enhancer, Strong TSS-distal (En-Sd), Strong TSS-proximal (En-Sp), Weak (En-W), Poised TSS-distal (En-Pd) and Poised TSS-proximal (En-Pp); Heterochromatin, Polycomb-associated (Hc-P) and H3K9me3-associated (Hc-H); No significant signal (NS).