Distinct epigenomic landscapes of pluripotent and lineage-committed human cells

R. David Hawkins, Gary C. Hon, Leonard K. Lee, Queminh Ngo, Ryan Lister, Mattia Pelizzola, Lee E. Edsall, Samantha Kuan, Ying Luu, Sarit Klugman, Jessica Antosiewicz-Bourget, Zhen Ye, Celso Espinoza, Saurabh Agarwahl, Li Shen, Victor Ruotti, Wei Wang, Ron Stewart, James A. Thomson, Joseph R. EckerBing Ren

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508 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)479-491
Number of pages13
JournalCell Stem Cell
Volume6
Issue number5
DOIs
StatePublished - May 7 2010

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ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

Cite this

Hawkins, R. D., Hon, G. C., Lee, L. K., Ngo, Q., Lister, R., Pelizzola, M., Edsall, L. E., Kuan, S., Luu, Y., Klugman, S., Antosiewicz-Bourget, J., Ye, Z., Espinoza, C., Agarwahl, S., Shen, L., Ruotti, V., Wang, W., Stewart, R., Thomson, J. A., ... Ren, B. (2010). Distinct epigenomic landscapes of pluripotent and lineage-committed human cells. Cell Stem Cell, 6(5), 479-491. https://doi.org/10.1016/j.stem.2010.03.018