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Polycomb complexes repress developmental regulators in murine embryonic stem cells

Author

Listed:
  • Laurie A. Boyer

    (Whitehead Institute for Biomedical Research)

  • Kathrin Plath

    (Whitehead Institute for Biomedical Research
    David Geffen School of Medicine at UCLA, 36-133 CHS)

  • Julia Zeitlinger

    (Whitehead Institute for Biomedical Research)

  • Tobias Brambrink

    (Whitehead Institute for Biomedical Research)

  • Lea A. Medeiros

    (Whitehead Institute for Biomedical Research
    Massachusetts Institute of Technology)

  • 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
    Massachusetts Institute of Technology)

  • Rudolf Jaenisch

    (Whitehead Institute for Biomedical Research
    Massachusetts Institute of Technology)

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.

Suggested Citation

  • 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. , 2006. "Polycomb complexes repress developmental regulators in murine embryonic stem cells," Nature, Nature, vol. 441(7091), pages 349-353, May.
  • Handle: RePEc:nat:nature:v:441:y:2006:i:7091:d:10.1038_nature04733
    DOI: 10.1038/nature04733
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    Cited by:

    1. Damiano Mangoni & Alessandro Simi & Pierre Lau & Alexandros Armaos & Federico Ansaloni & Azzurra Codino & Devid Damiani & Lavinia Floreani & Valerio Carlo & Diego Vozzi & Francesca Persichetti & Claud, 2023. "LINE-1 regulates cortical development by acting as long non-coding RNAs," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    2. Natalia Benetti & Quentin Gouil & Andres Tapia del Fierro & Tamara Beck & Kelsey Breslin & Andrew Keniry & Edwina McGlinn & Marnie E. Blewitt, 2022. "Maternal SMCHD1 regulates Hox gene expression and patterning in the mouse embryo," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    3. M S Vijayabaskar & Debbie K Goode & Nadine Obier & Monika Lichtinger & Amber M L Emmett & Fatin N Zainul Abidin & Nisar Shar & Rebecca Hannah & Salam A Assi & Michael Lie-A-Ling & Berthold Gottgens & , 2019. "Identification of gene specific cis-regulatory elements during differentiation of mouse embryonic stem cells: An integrative approach using high-throughput datasets," PLOS Computational Biology, Public Library of Science, vol. 15(11), pages 1-29, November.
    4. Marco D. Carpenter & Delaney K. Fischer & Shuo Zhang & Allison M. Bond & Kyle S. Czarnecki & Morgan T. Woolf & Hongjun Song & Elizabeth A. Heller, 2022. "Cell-type specific profiling of histone post-translational modifications in the adult mouse striatum," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    5. Tara N. Yankee & Sungryong Oh & Emma Wentworth Winchester & Andrea Wilderman & Kelsey Robinson & Tia Gordon & Jill A. Rosenfeld & Jennifer VanOudenhove & Daryl A. Scott & Elizabeth J. Leslie & Justin , 2023. "Integrative analysis of transcriptome dynamics during human craniofacial development identifies candidate disease genes," Nature Communications, Nature, vol. 14(1), pages 1-23, December.
    6. Jacob Bergstedt & Sadoune Ait Kaci Azzou & Kristin Tsuo & Anthony Jaquaniello & Alejandra Urrutia & Maxime Rotival & David T. S. Lin & Julia L. MacIsaac & Michael S. Kobor & Matthew L. Albert & Darrag, 2022. "The immune factors driving DNA methylation variation in human blood," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    7. Fiona G G Nielsen & Kasper Galschiøt Markus & Rune Møllegaard Friborg & Lene Monrad Favrholdt & Hendrik G Stunnenberg & Martijn Huynen, 2012. "CATCHprofiles: Clustering and Alignment Tool for ChIP Profiles," PLOS ONE, Public Library of Science, vol. 7(1), pages 1-8, January.
    8. Shijia Zhu & Guohua Wang & Bo Liu & Yadong Wang, 2013. "Modeling Exon Expression Using Histone Modifications," PLOS ONE, Public Library of Science, vol. 8(6), pages 1-15, June.

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