Genome-wide DNA Methylation Analysis

500 ng of DNA from each sample was bisulfite converted using the EZ DNA Methylation™ Kit (Zymo Research, USA) as previously described [6 (link)]. DNA methylation was evaluated by hybridizing bisulfite-converted DNA to the Infinium HumanMethylation450 BeadChips (Illumina, USA) according to manufacturer’s directions. The Infinium array interrogates over 485,000 methylation sites across the human genome, covering 96 % of CpG islands, shores and flanking regions as well as 99 % of RefSeq genes with an average of 17 CpG sites per gene region. The array covers the promoter, 5′-untranslated region, first exon, gene body, and 3′-untranslated region of each gene. Array hybridization of the bisulfite-converted DNA was performed at the University of Michigan DNA Sequencing Core.