Fig. 5: Epigenomic rejuvenation of the dorsal hippocampus in enriched environments.

a UpSet plots showing the intersections between aging and EEall ChIP-seq DERs (unadjusted p < 0.05, two sided Wald tests) for each histone modification. b Heatmap summarizing the significant (FDR < 0.05, one-sided Fisher’s exact tests) intersections between aging and EEall ChIP-seq DERs (unadjusted p < 0.05, two sided Wald tests) across all histone modifications. Significant intersections are coloured on the basis of their odds ratio. c Bar plots describing the numbers of curated DERs which display EE-associated rejuvenation of aging alterations in old samples. d Heatmap showing the significant intersections (FDR < 0.05 for one-sided permutation regioneR tests) between curated rejuvenation DERs and curated rejuvenation DEGs. Significant intersections are coloured by log2(fold enrichment). e, f Genomic plots indicating, in the upper panels, the distribution of epigenomic marks (5mC, ATAC-seq, histone post-translational modifications) across the bodies of the Pcdh15 (e) and Ror1 (f) genes. The measurements shown are either DNA methylation values for EM-seq profiled CpGs or log-CPM values (200 bp bins and normalized to [0–1] scale) for ATAC-seq and ChIP-seq, while the lower tracks represent genes, CpG Islands and ENCODE murine forebrain P0 enhancer elements. Below, highlighted from the upper plots are regions curated as rejuvenated in old samples, and the log-CPM values are shown across the groups accompanied by the difference in log-CPM between old samples and the rest of samples. Finally, the bottom boxplots show the RNA-seq and ChIP-seq values for the gene and the whole region in VST units (n = 3 for all RNA-seq groups and n = 2 for all ChIP-seq groups, the reju-DERs and reju-DEGs were defined as stated in Methods). 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.