Research Paper Volume 15, Issue 14 pp 6690—6709

Figure 3. Age-related methylation-change pattern is linked to the CpG density of the region. (A) Different types of methylation change in areas with varying CpG densities. Promoter regions were divided into five groups based on the CpG density: 5≤CpG<10, 10≤CpG<20, 20≤CpG<50, 50≤CpG<10, or 100≤CpG<250. The number of corresponding promoter regions is denoted by each density category. The arrows represent the CpG-density-dependent increase (hypermethylation) or decrease of methylation (hypomethylation). (B) CpG density-based classification of chromosomal CpG sites as low (L, 0–5 CpGs; Q1 >50% methylation), high (H, >12; Q3 <50%), and moderate (M, 6-12; the remainder), respectively. CpG density was determined by counting the number of CpG dinucleotides within 200 bp of a single CpG (top). Box plots show the distribution of methylation levels for CpG sites with identical CpG density. (C) Distribution of methylation levels of CpGs in the CpG-density classification groups. Each CpG site is classified as one of the following: HH, HM, HL, MH, MM, ML, LH, LN, or LL. The red dots indicate the average methylations. (D) The number of CpG sites assigned to each classification. (E) Different patterns of age-linked methylation changes at differently classified CpG sites.