Global epigenetic changes during somatic cell reprogramming to iPS cells

Anna Mattout, Alva Biran, Eran Meshorer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

92 Scopus citations

Abstract

Embryonic stem cells (ESCs) exhibit unique chromatin features, including a permissive transcriptional program and an open, decondensed chromatin state. Induced pluripotent stem cells (iPSCs), which are very similar to ESCs, hold great promise for therapy and basic research. However, the mechanisms by which reprogramming occurs and the chromatin organization that underlies the reprogramming process are largely unknown. Here we characterize and compare the epigenetic landscapes of partially and fully reprogrammed iPSCs to mouse embryonic fibroblasts (MEFs) and ESCs, which serves as a standard for pluripotency. Using immunofluorescence and biochemical fractionations, we analyzed the levels and distribution of a battery of histone modifications (H3ac, H4ac, H4K5ac, H3K9ac, H3K27ac, H3K4me3, H3K36me2, H3K9me3, H3K27me3, and γH2AX), as well as HP1α and lamin A. We find that fully reprogrammed iPSCs are epigenetically identical to ESCs, and that partially reprogrammed iPSCs are closer to MEFs. Intriguingly, combining both time-course reprogramming experiments and data from the partially reprogrammed iPSCs, we find that heterochromatin reorganization precedes Nanog expression and active histone marking. Together, these data delineate the global epigenetic state of iPSCs in conjunction with their pluripotent state, and demonstrate that heterochromatin precedes euchromatin in reorganization during reprogramming.

Original languageAmerican English
Pages (from-to)341-350
Number of pages10
JournalJournal of Molecular Cell Biology
Volume3
Issue number6
DOIs
StatePublished - Dec 2011

Keywords

  • ESCs
  • chromatin
  • epigenetics
  • histone modifications
  • iPSCs
  • pluripotency
  • reprogramming

Fingerprint

Dive into the research topics of 'Global epigenetic changes during somatic cell reprogramming to iPS cells'. Together they form a unique fingerprint.

Cite this