Reprogramming factor expression initiates widespread targeted chromatin remodeling

Richard P. Koche, Zachary D. Smith, Mazhar Adli, Hongcang Gu, Manching Ku, Andreas Gnirke, Bradley E. Bernstein, Alexander Meissner*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

260 Scopus citations

Abstract

Despite rapid progress in characterizing transcription factor-driven reprogramming of somatic cells to an induced pluripotent stem cell (iPSC) state, many mechanistic questions still remain. To gain insight into the earliest events in the reprogramming process, we systematically analyzed the transcriptional and epigenetic changes that occur during early factor induction after discrete numbers of divisions. We observed rapid, genome-wide changes in the euchromatic histone modification, H3K4me2, at more than a thousand loci including large subsets of pluripotency-related or developmentally regulated gene promoters and enhancers. In contrast, patterns of the repressive H3K27me3 modification remained largely unchanged except for focused depletion specifically at positions where H3K4 methylation is gained. These chromatin regulatory events precede transcriptional changes within the corresponding loci. Our data provide evidence for an early, organized, and population-wide epigenetic response to ectopic reprogramming factors that clarify the temporal order through which somatic identity is reset during reprogramming.

Original languageEnglish (US)
Pages (from-to)96-105
Number of pages10
JournalCell stem cell
Volume8
Issue number1
DOIs
StatePublished - Jan 7 2011
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

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