Letter abstract
Nature Genetics
Published online: 1 November 2009 | doi:10.1038/ng.471
Differential methylation of tissue- and cancer-specific CpG island shores distinguishes human induced pluripotent stem cells, embryonic stem cells and fibroblasts
Akiko Doi1,5, In-Hyun Park2,5, Bo Wen1,5, Peter Murakami1, Martin J Aryee3,4, Rafael Irizarry3, Brian Herb1, Christine Ladd-Acosta1, Junsung Rho2, Sabine Loewer2, Justine Miller2, Thorsten Schlaeger2, George Q Daley2,6 & Andrew P Feinberg1,6
Abstract
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.
- Center for Epigenetics and Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
- Division of Pediatric Hematology/Oncology, Children's Hospital Boston and Howard Hughes Medical Institute, Boston, Massachusetts, USA.
- Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA.
- These authors contributed equally to this work.
- These authors jointly supervised this work.
Correspondence to: George Q Daley2,6 e-mail: George.Daley@childrens.harvard.edu
Correspondence to: Andrew P Feinberg1,6 e-mail: afeinberg@jhu.edu
