Identification of novel imprinted differentially methylated regions by global analysis of human-parthenogenetic-induced pluripotent stem cells

Yonatan Stelzer, Daniel Ronen, Christoph Bock, Patrick Boyle, Alexander Meissner*, Nissim Benvenisty

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Parental imprinting is an epigenetic phenomenon by which genes are expressed in a monoallelic fashion, according to their parent of origin. DNA methylation is considered the hallmark mechanism regulating parental imprinting. To identify imprinted differentially methylated regions (DMRs), we compared the DNA methylation status between multiple normal and parthenogenetic human pluripotent stem cells (PSCs) by performing reduced representation bisulfite sequencing. Our analysis identified over 20 previously unknown imprinted DMRs in addition to the known DMRs. These include DMRs in loci associated with human disorders, and a class of intergenic DMRs that do not seem to be related to gene expression. Furthermore, the study showed some DMRs to be unstable, liable to differentiation or reprogramming. A comprehensive comparison between mouse and human DMRs identified almost half of the imprinted DMRs to be species specific. Taken together, our data map novel DMRs in the human genome, their evolutionary conservation, and relation to gene expression.

Original languageAmerican English
Pages (from-to)79-89
Number of pages11
JournalStem Cell Reports
Volume1
Issue number1
DOIs
StatePublished - 2013

Bibliographical note

Funding Information:
The authors would like to thank Tamar Golan-Lev for her assistance with the graphic design. N.B. is the Herbert Cohn Chair in Cancer Research. This research was supported by The Legacy Heritage Biomedical Program of the Israel Science Foundation (grant No. 1252/12), and by the Centers of Excellence Legacy Heritage Biomedical Science Partnership (grants No. 1801/10). D.R. is supported by the Lady Davis Fellowship Trust and the Israel Cancer Research Fund. A.M. is a New York Stem Cell Foundation Robertson Investigator. Part of this work was funded by NIH grants (U01ES017155 and P01GM099117) and The New York Stem Cell Foundation.

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