Figure 4.

Characterization of differentially methylated regions (DMRs). (A) Hypermethylated and hypomethylated DMRs show distinct chromatin states. DMRs that become hypermethylated in old epidermis (hyperDMRs) are enriched for H3K4me3 and H3K27me3, while DMRs that become hypomethylated in old epidermis (hypoDMRs) are enriched for H3K27ac. Numbers below the x-axis indicate the distance from the center of the DMR (dashed vertical line) in bp. (B) Enrichment of DMRs within defined genome segments. Bars indicate the ratio of the observed DMR frequency and the average frequency across the genome. Blue bars represent DMRs that are hypomethylated in the old epidermis, red bars represent DMRs that are hypermethylated in the old epidermis. (C) The ERBB receptor feedback inhibitor 1 (ERRFI1) promoter region harbors a representative DMR. ERRFI1 is required for proper epidermal homeostasis [30] and is expressed at lower levels in old epidermis samples (right panel, blue and red bars indicates expression in the young and old epidermis samples, respectively). Blue lines indicate methylation ratios in the young epidermis, red lines indicate methylation ratios in the old epidermis. The green bar indicates the position of the ERRFI1 promoter CpG island. (D) An annotated active enhancer element from the low-density lipoprotein receptor (LDLR) gene region harbors a DMR. Age-related methylation changes that were associated with lower expression levels of LDLR in the old sample (right panel, blue and red bars indicates expression in the young and old epidermis samples, respectively), which may promote the formation of Xanthelasma, a dermatological lesion often found in the elderly population.