Polycomb complexes repress developmental regulators in murine embryonic stem cells

Laurie A. Boyer, Kathrin Plath, Julia Zeitlinger, Tobias Brambrink, Lea A. Medeiros, Tong Ihn Lee, Stuart S. Levine, Marius Wernig, Adriana Tajonar, Mridula K. Ray, George W. Bell, Arie P. Otte, Miguel Vidal, David K. Gifford, Richard A. Young and Rudolf Jaenisch ()
Additional contact information
Laurie A. Boyer: Whitehead Institute for Biomedical Research
Kathrin Plath: Whitehead Institute for Biomedical Research
Julia Zeitlinger: Whitehead Institute for Biomedical Research
Tobias Brambrink: Whitehead Institute for Biomedical Research
Lea A. Medeiros: Whitehead Institute for Biomedical Research
Tong Ihn Lee: Whitehead Institute for Biomedical Research
Stuart S. Levine: Whitehead Institute for Biomedical Research
Marius Wernig: Whitehead Institute for Biomedical Research
Adriana Tajonar: Massachusetts Institute of Technology
Mridula K. Ray: Massachusetts Institute of Technology
George W. Bell: Whitehead Institute for Biomedical Research
Arie P. Otte: Swammerdam Institute for Life Sciences, University of Amsterdam
Miguel Vidal: Developmental and Cell Biology Centro de Investigaciones Biológicas (CSIC)
David K. Gifford: Massachusetts Institute of Technology
Richard A. Young: Whitehead Institute for Biomedical Research
Rudolf Jaenisch: Whitehead Institute for Biomedical Research

Nature, 2006, vol. 441, issue 7091, 349-353

Abstract: Abstract The mechanisms by which embryonic stem (ES) cells self-renew while maintaining the ability to differentiate into virtually all adult cell types are not well understood. Polycomb group (PcG) proteins are transcriptional repressors that help to maintain cellular identity during metazoan development by epigenetic modification of chromatin structure1. PcG proteins have essential roles in early embryonic development2,3,4,5,6 and have been implicated in ES cell pluripotency2, but few of their target genes are known in mammals. Here we show that PcG proteins directly repress a large cohort of developmental regulators in murine ES cells, the expression of which would otherwise promote differentiation. Using genome-wide location analysis in murine ES cells, we found that the Polycomb repressive complexes PRC1 and PRC2 co-occupied 512 genes, many of which encode transcription factors with important roles in development. All of the co-occupied genes contained modified nucleosomes (trimethylated Lys 27 on histone H3). Consistent with a causal role in gene silencing in ES cells, PcG target genes were de-repressed in cells deficient for the PRC2 component Eed, and were preferentially activated on induction of differentiation. Our results indicate that dynamic repression of developmental pathways by Polycomb complexes may be required for maintaining ES cell pluripotency and plasticity during embryonic development.

Date: 2006
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DOI: 10.1038/nature04733

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