Integrative Analysis of Methylome and Transcriptome Reveals the Importance of Unmethylated CpGs in Non-CpG Island Gene Activation
Figure 1
Association between expression levels and promoter methylation. All genes in ES cells were divided into CpG island (a, b) and nonisland (non-CGI) (c, d) genes. The genes in each category were sorted according to the number of pGs (a, c) and pGs (b, d) in their promoter sequence, and the sorted lists were divided into 10 equally sized bins (765 and 429 genes in each bin of the CGI and non-CGI, resp.). Genes in each bin were resorted according to their expression level and the cumulative distribution is shown. The bins are numbered according to the increasing number of pGs (a, c) and pGs (b, d). The insert in each graph presents the median expression value plotted as a function of the median methylation level in each bin for pGs and pGs. Spearman Rho and values were not significant in (a), (b), and (d) (,, , , and , resp.) and were highly significant (, ) in (c). Note that the gradual increase in expression in association with a gradual increase in pG counts is seen in the medians, and thus it is not likely that it is the result of a contamination of nonannotated CGI genes (see Discussion). Essentially the same results were obtained with a different set of methylome and transcriptome data [13] (Figure S12).
