Fig. 1

Discovery and characterization of differentially methylated regions (DMRs) in aging livers by whole-genome bisulfite sequencing (WGBS). A Histograms of CpG event frequencies categorized by their DNA methylation levels for three baseline age groups (A2R0, A8R0, and A16R0), where the X-axis shows the DNA methylation level (from 0 to 100%) and the Y-axis shows the CpG event frequency. Each graph represents the average of four biological samples. B Heat maps of aging DMRs by comparing 8-m/o (A8R0) to 2-m/o (A2R0) livers (B1), 16-m/o (A16R0) to A8R0 livers (B2), and A16R0 to A2R0 livers (B3). Color scale indicates Z score, showing increased or decreased methylation by red or green color, respectively. Hyper-DMRs are listed on top of hypo-DMRs. R0 indicates the non-regenerative condition. C Genomic distributions of hypo-DMRs (grey bars) and hyper-DMRs (black bars) in comparing A8R0-to-A2R0, A16R0-to-A8R0, or A16R0-to-A2R0 livers. Abbreviations: rsmk, repetitive DNA regions; gBody, gene body; TSS, transcription start site; rep, repeat; SINE, short interspersed nuclear elements; LINE, long interspersed nuclear elements; UTR, untranslated region. Y-axis indicates the percentage (%) of total hypo-DMRs or hyper-DMRs found in specific genomic regions of interest (hotspot analysis, see the “Methods” section). Different genomic regions are not mutually exclusive. D Pie charts of aging DMR percentages found in genomic regions containing gene structures versus intergenic regions (D1) or in repeat versus non-repeat sequences (D2). Abbreviations: TSS-7 k, within 7kB upstream of TSS; GB, gene body; IG, intergenic region; LINE, long interspersed nuclear elements; SINE, short interspersed nuclear elements; SimRep: simple repeats (micro-satellites); Satellite, satellite repeats; Others: other repeat categories as defined in RMSK from the UCSC genome browser (https://genome.ucsc.edu/cgi-bin/hgTables?db=hg38&hgta_group=rep&hgta_track=rmsk&hgta_table=rmsk&hgta_doSchema=describe+table+schema); nonRep: non-repeat regions