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Differential methylation of tissue- and cancer-specific CpG island shores distinguishes human induced pluripotent stem cells, embryonic stem cells and fibroblasts

Open access
Doi, Akiko, Park, In-Hyun, Wen, Bo, Murakami, Peter, Aryee, Martin J, Irizarry, Rafael, Herb, Brian, Ladd-Acosta, Christine, Rho, Junsung, Loewer, Sabine, Miller, Justine, Schlaeger, Thorsten, Daley, George Q, Feinberg, Andrew P·2009·Nature Genetics

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.

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Metadata

Authors
Doi, A., Park, I.-H., Wen, B., Murakami, P., Aryee, M. J., Irizarry, R., Herb, B., Ladd-Acosta, C., Rho, J., Loewer, S., Miller, J., Schlaeger, T., Daley, G. Q., & Feinberg, A. P.
Venue
Nature Genetics
Published
2009-11-01
Volume
41
Issue
12
Pages
1350-1353
ISSN
  • 1061-4036 (ISSN-L)
  • 1546-1718
OpenAlex
W2065751798
Cited by
1,177
References
5
FWCI
48.01
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Differential methylation of tissue- and cancer-specific CpG island shores distinguishes human induced pluripotent stem cells, embryonic stem cells and fibroblasts. https://app.cochat.ai/papers/10.1038/ng.471
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Doi, A., Park, I.-H., Wen, B., Murakami, P., Aryee, M. J., Irizarry, R., Herb, B., Ladd-Acosta, C., Rho, J., Loewer, S., Miller, J., Schlaeger, T., Daley, G. Q., & Feinberg, A. P. (2009). Differential methylation of tissue- and cancer-specific CpG island shores distinguishes human induced pluripotent stem cells, embryonic stem cells and fibroblasts. Nature Genetics. https://doi.org/10.1038/ng.471

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