title: Differential methylation of tissue- and cancer-specific CpG island shores distinguishes human induced pluripotent stem cells, embryonic stem cells and fibroblasts.
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.
authors.affiliation: Center for Epigenetics and Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Akiko
authors.initials: A
authors.lastname: Doi
authors.forename: In-Hyun
authors.initials: IH
authors.lastname: Park
authors.forename: Bo
authors.initials: B
authors.lastname: Wen
authors.forename: Peter
authors.initials: P
authors.lastname: Murakami
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Aryee
authors.forename: Rafael
authors.initials: R
authors.lastname: Irizarry
authors.forename: Brian
authors.initials: B
authors.lastname: Herb
authors.forename: Christine
authors.initials: C
authors.lastname: Ladd-Acosta
authors.forename: Junsung
authors.initials: J
authors.lastname: Rho
authors.forename: Sabine
authors.initials: S
authors.lastname: Loewer
authors.forename: Justine
authors.initials: J
authors.lastname: Miller
authors.forename: Thorsten
authors.initials: T
authors.lastname: Schlaeger
authors.forename: George Q
authors.initials: GQ
authors.lastname: Daley
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Feinberg
mesh_terms: D002454:Cell Differentiation; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D044127:Epigenesis, Genetic; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics