Meta-analysis of human methylomes reveals stably methylated sequences surrounding CpG islands associated with high gene expression.

摘要: DNA methylation is thought to play an important role in the regulation of mammalian gene expression, partly based on observation that a lack CpG island promoters associated with high transcriptional activity. However, level only accounts for fraction variance and other domains hypothesized role. We regions very stability would exist provide biological insight into both within outside islands. set out identify highly stable human methylome, subset CpGs assayed Illumina Infinium 450 K array. Using 1,737 samples from 30 publically available studies, we identified 15,224 are ‘ultrastable’ their state across tissues developmental stages (974 always methylated; 14,250 unmethylated). Further analysis ultrastable led us novel islands, ‘ravines’, which exhibit markedly consistent pattern low methylated flanking shores shelves. distinguish ravines islands characterized by broader region methylation. Interestingly, higher expression compared typical unmethylated more often found near housekeeping genes. The identification sites methylome subclass encompassing regions, established early development maintained through differentiation. This particularly levels providing new evidence beyond could expression.