The hypermethylation of early-replicating regions is predominantly due to gene-body hypermethylation. We tested how gene-body methylation could be contributing to the patterns shown in Figure 2, reproducing the fibroblast plot to facilitate comparison in A. C shows the results when 100-kb windows that do not contain genes are removed, with a decrease in the late-replicating/hypomethylated population of signals. Excluding gene bodies, to study only intergenic methylation, generates a shift in signal distribution toward hypomethylated DNA (B), especially when the analysis is restricted to the gene-containing regions of the genome (D). These results show that a substantial proportion of the correlation of cytosine methylation with early replication is due to the methylation targeting transcribed sequences.
