The researchers analyzed 42 different WGBS data sets, which consisted of 30 different normal and disease human cell and tissue types, including human embryonic stem (ES) cells and ES cell-derived cells, primary human cells, cells that had been in culture for long periods of time, and cells from human disease conditions such as cancer. Using relatively stringent criteria for changes in DNA methylation (≥ 30% difference in methylation levels), and focusing on the “developmental” sample set (which excluded long-term cultured cells and the disease state cells), the authors identified ~5.6 million “dynamic” CpG sites in the human genome, which is only 21.8% of the total autosomal CpG sites investigated. This means that the DNA methylation status for the remaining ~80% of the CpG sites in the human genome is pretty static and does not change significantly between different tissue types or developmental states. Of these highly dynamic differentially methylated regions (DMRs), most of them (~70%) show high levels of methylation, and only very few (~2%) have low levels of DNA methylation, suggesting that CpG sites that are already methylated generally show the most dynamic changes, rather than normally unmethylated sites becoming methylated in some cases.
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