Distinct Epigenomic Landscapes of Pluripotent and Lineage-Committed Human Cells

Cell Stem Cell. 2010 May 7;6(5):479-91. doi: 10.1016/j.stem.2010.03.018.

Abstract

Human embryonic stem cells (hESCs) share an identical genome with lineage-committed cells, yet possess the remarkable properties of self-renewal and pluripotency. The diverse cellular properties in different cells have been attributed to their distinct epigenomes, but how much epigenomes differ remains unclear. Here, we report that epigenomic landscapes in hESCs and lineage-committed cells are drastically different. By comparing the chromatin-modification profiles and DNA methylomes in hESCs and primary fibroblasts, we find that nearly one-third of the genome differs in chromatin structure. Most changes arise from dramatic redistributions of repressive H3K9me3 and H3K27me3 marks, which form blocks that significantly expand in fibroblasts. A large number of potential regulatory sequences also exhibit a high degree of dynamics in chromatin modifications and DNA methylation. Additionally, we observe novel, context-dependent relationships between DNA methylation and chromatin modifications. Our results provide new insights into epigenetic mechanisms underlying properties of pluripotency and cell fate commitment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cell Lineage / genetics*
  • Chromatin / genetics
  • CpG Islands / genetics
  • DNA Methylation / genetics
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / metabolism
  • Epigenesis, Genetic*
  • Fibroblasts / cytology*
  • Fibroblasts / metabolism*
  • Genes, Developmental
  • Genome, Human / genetics*
  • Histones / metabolism
  • Humans
  • Lysine / metabolism
  • Pluripotent Stem Cells / cytology*
  • Pluripotent Stem Cells / metabolism*
  • Protein Processing, Post-Translational
  • Regulatory Sequences, Nucleic Acid / genetics

Substances

  • Chromatin
  • Histones
  • Lysine