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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1350-1353
Number of pages4
JournalNature Genetics
Volume41
Issue number12
DOIs
StatePublished - Dec 2009

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Induced Pluripotent Stem Cells
Cytosine
Guanine
Embryonic Stem Cells
Islands
Methylation
Fibroblasts
Phosphates
Epigenomics
Colonic Neoplasms
Neoplasms
DNA Methylation
Chromatin
Spleen
Genome
Cell Line
Liver
Brain

ASJC Scopus subject areas

  • Genetics

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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. / Doi, Akiko; Park, In Hyun; Wen, Bo; Murakami, Peter; Aryee, Martin J.; Irizarry, Rafael; Herb, Brian; Ladd-Acosta, Christine Marie; Rho, Junsung; Loewer, Sabine; Miller, Justine; Schlaeger, Thorsten; Daley, George Q.; Feinberg, Andrew P.

In: Nature Genetics, Vol. 41, No. 12, 12.2009, p. 1350-1353.

Research output: Contribution to journalArticle

Doi, A, Park, IH, Wen, B, Murakami, P, Aryee, MJ, Irizarry, R, Herb, B, Ladd-Acosta, CM, Rho, J, Loewer, S, Miller, J, Schlaeger, T, Daley, GQ & Feinberg, AP 2009, 'Differential methylation of tissue-and cancer-specific CpG island shores distinguishes human induced pluripotent stem cells, embryonic stem cells and fibroblasts', Nature Genetics, vol. 41, no. 12, pp. 1350-1353. https://doi.org/10.1038/ng.471
Doi, Akiko ; Park, In Hyun ; Wen, Bo ; Murakami, Peter ; Aryee, Martin J. ; Irizarry, Rafael ; Herb, Brian ; Ladd-Acosta, Christine Marie ; Rho, Junsung ; Loewer, Sabine ; Miller, Justine ; Schlaeger, Thorsten ; Daley, George Q. ; Feinberg, Andrew P. / Differential methylation of tissue-and cancer-specific CpG island shores distinguishes human induced pluripotent stem cells, embryonic stem cells and fibroblasts. In: Nature Genetics. 2009 ; Vol. 41, No. 12. pp. 1350-1353.
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