Differential methylation of tissue- and cancer-specific CpG island shores distinguishes human induced pluripotent stem cells, embryonic stem cells and fibroblasts.
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.
Doi
Akiko
A
Center for Epigenetics and Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Park
In-Hyun
IH
Wen
Bo
B
Murakami
Peter
P
Aryee
Martin J
MJ
Irizarry
Rafael
R
Herb
Brian
B
Ladd-Acosta
Christine
C
Rho
Junsung
J
Loewer
Sabine
S
Miller
Justine
J
Schlaeger
Thorsten
T
Daley
George Q
GQ
Feinberg
Andrew P
AP
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