Induced pluripotent stem (iPS) cells are derived by epigenetic reprogramming, 
but their DNA methylation patterns have not yet been analyzed on a genome-wide 
scale. Here, we find substantial hypermethylation and hypomethylation of 
cytosine-phosphate-guanine (CpG) island shores in nine human iPS cell lines as 
compared to their parental fibroblasts. The differentially methylated regions 
(DMRs) in the reprogrammed cells (denoted R-DMRs) were significantly enriched in 
tissue-specific (T-DMRs; 2.6-fold, P < 10(-4)) and cancer-specific DMRs (C-DMRs; 
3.6-fold, P < 10(-4)). Notably, even though the iPS cells are derived from 
fibroblasts, their R-DMRs can distinguish between normal brain, liver and spleen 
cells and between colon cancer and normal colon cells. Thus, many DMRs are 
broadly involved in tissue differentiation, epigenetic reprogramming and cancer. 
We observed colocalization of hypomethylated R-DMRs with hypermethylated C-DMRs 
and bivalent chromatin marks, and colocalization of hypermethylated R-DMRs with 
hypomethylated C-DMRs and the absence of bivalent marks, suggesting two 
mechanisms for epigenetic reprogramming in iPS cells and cancer.