Block hypomethylation progresses from younger sun-protected to older sun-protected to younger sun-exposed to older sun-exposed tissue. (A) Example of a region identified as a block comparing older sun-exposed to younger sun-protected epidermal samples using 450k data. Top panel: methylation beta values (Methylated signal/Total signal) for 'collapsed' measurements of methylation from open sea probes in 450k data. These are methylation averages for each 1,500 bp open sea region calculated as part of the minfi’s 'block finder' algorithm. The points represent individual samples at each location, dotted lines show smoothed measurements across the region for each individual and solid lines represent the smoothed average for each group. The box demarcates the block identified using Minfi. Bottom panel: smoothed methylation beta values from WGBS data within the regions identified in 450k analysis. Horizontal bars indicate the locations of hypomethylated blocks identified previously in cancer and heterochromatin LOCKs . (B) Example of a region identified as a block comparing older, sun-exposed and younger, sun-protected epidermal samples using 450k data, plotted as in (A). (C) Heatmap showing mean block methylation in all blocks identified comparing O-exp and Y-pro epidermis. Samples are ordered by mean methylation, and blocks are ordered by mean difference in methylation between O-exp and Y-pro samples. Red/yellow indicate lower/higher mean methylation levels, respectively. (D) Relationship between block methylation and Griffiths’ photoage grade. Mean methylation within all blocks identified comparing O-exp and Y-pro epidermis, versus Griffiths’ photoage grade assigned to the sample donor.