A survey of DNA methylation polymorphism identifies environmentally responsive co-regulated networks ofepigenetic variation in the human genome

Understanding the causes and consequences of genomic variation is a major goal in the field of genetics. While studies such as the Hapmap and 1000 Genomes Projects have resulted in detailed maps of genetic variation, to date there are no robust maps of epigenetic variation in humans, and as a result few insights have been made into their significance or underlying biology. Here we set out to define and characterize sites of common epigenetic variation in humans, that we term Variable Methylation Regions (VMRs). Using a robust approach we identify hundreds of VMRs in each cell type that show common variability in DNA methylation levels in the normal population. Human fibroblast cells from GM04503 individual were grown to various levels of growth and confluency reflecting cellular stress. Cells were harvested after 3, 5, 7, 10 and 12 days of growth (TP 1-5) where the medium was changed every two days to maintain optimal growth. A subset of cells were grown in parallel and harvested at exactly the same time points however the media were left unchanged to promote cellular stress. From each treatment, whole DNA was extracted and global DNA methylation levels were assessed using Illumina Infinium HumanMethylation450 BeadChip.