Global indiscriminate methylation in cell-specific gene promoters following reprogramming into human induced pluripotent stem cells

Jonathan Nissenbaum, Ori Bar-Nur, Eyal Ben-David, Nissim Benvenisty

Research output: Contribution to journalArticlepeer-review

Abstract

Molecular reprogramming of somatic cells into human induced pluripotent stem cells (iPSCs) is accompanied by extensive changes in gene expression patterns and epigenetic marks. To better understand the link between gene expression and DNA methylation, we have profiled human somatic cells from different embryonic cell types (endoderm, mesoderm, and parthenogenetic germ cells) and the iPSCs generated from them. We show that reprogramming is accompanied by extensive DNA methylation in CpG-poor promoters, sparing CpG-rich promoters. Intriguingly, methylation in CpG-poor promoters occurred not only in downregulated genes, but also in genes that are not expressed in the parental somatic cells or their respective iPSCs. These genes are predominantly tissue-specific genes of other cell types from different lineages. Our results suggest a role of DNA methylation in the silencing of the somatic cell identity by global nonspecific methylation of tissue-specific genes from all lineages, regardless of their expression in the parental somatic cells.

Original languageEnglish
Pages (from-to)509-517
Number of pages9
JournalStem Cell Reports
Volume1
Issue number6
DOIs
StatePublished - 17 Dec 2013

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

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