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Your Environment. Your Health.

DNA Methylation in the Human Genome

Bradley E. Bernstein, M.D., Ph.D.; Alex Meissner, Ph.D.
Broad Institute of MIT and Harvard
NIEHS Grant U01ES017155

DNA methylation regulates the expression of genes that guide development and define cell types. In mammals, 70 to 80 percent of all cytidine-phosphateguanosine (CpG) dinucleotides are methylated, but NIEHS-supported researchers report evidence that only a fraction of these CpGs likely participate in genome regulation in a developmental context. The DNA methylation signatures, called differentially methylated regions, that the researchers identified can be used to guide new, more effective approaches that examine only the most informative portion of CpGs.

The researchers systematically investigated the DNA methylation of 42 whole-genome bisulphite sequencing data sets across 30 diverse human cell and tissue types. For cells and tissue undergoing normal development, they observed dynamic regulation for only 21.8 percent of autosomal CpGs. Genome-wide association studies showed that differentially methylated regions often contained single nucleotide polymorphisms associated with cancer and Alzheimer’s disease. The investigators used their set of differentially methylated regions to correctly identify an unknown tissue sample and to classify the types of cell present in a heterogeneous sample.

Citation: Ziller MJ, Gu H, Müller F, Donaghey J, Tsai LT, Kohlbacher O, De Jager PL, Rosen ED, Bennett DA, Bernstein BE, Gnirke A, Meissner A. 2013. Charting a dynamic DNA methylation landscape of the human genome. Nature 500(7463):477-481.