1. Chromosomes and Gene Expression
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RYBP stimulates PRC1 to shape chromatin-based communication between Polycomb repressive complexes

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Cite this article as: eLife 2016;5:e18591 doi: 10.7554/eLife.18591

Abstract

Polycomb group (PcG) proteins function as chromatin-based transcriptional repressors that are essential for normal gene regulation during development. However, how these systems function to achieve transcriptional regulation remains very poorly understood. Here, we discover that the histone H2AK119 E3 ubiquitin ligase activity of Polycomb repressive complex 1(PRC1) is defined by the composition of its catalytic subunits and is highly regulated by RYBP/YAF2-dependent stimulation. In mouse embryonic stem cells, RYBP plays a central role in shaping H2AK119 mono-ubiquitylation at PcG targets and underpins an activity-based communication between PRC1 and Polycomb repressive complex 2(PRC2) which is required for normal histone H3 lysine 27 trimethylation(H3K27me3). Without normal histone modification-dependent communication between PRC1 and PRC2, repressive Polycomb chromatin domains can erode, rendering target genes susceptible to inappropriate gene expression signals. This suggests that activity-based communication and histone modification-dependent thresholds create a localized form of epigenetic memory required for normal PcG chromatin domain function in gene regulation.

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Article and author information

Author details

  1. Nathan R Rose

    Department of Biochemistry, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Hamish W King

    Department of Biochemistry, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Neil P Blackledge

    Department of Biochemistry, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Nadezda A Fursova

    Department of Biochemistry, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Katherine JI Ember

    Department of Biochemistry, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Roman Fischer

    TDI Mass Spectrometry Laboratory, Target Discovery Institute, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9715-5951
  7. Benedikt M Kessler

    TDI Mass Spectrometry Laboratory, Target Discovery Institute, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  8. Robert J Klose

    Department of Biochemistry, University of Oxford, Oxford, United Kingdom
    For correspondence
    rob.klose@bioch.ox.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8726-7888

Funding

European Research Council (Consolidator grant, 681440)

  • Robert J Klose

Wellcome (Senior Research Fellowship, 098024/Z/11/Z)

  • Robert J Klose

Lister Institute of Preventive Medicine

  • Robert J Klose

Wellcome (097813/Z/11/Z)

  • Benedikt M Kessler

John Fell Fund, University of Oxford (133/075)

  • Benedikt M Kessler

Kennedy Memorial Trust

  • Benedikt M Kessler

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Peter Verrijzer, Erasmus University Medical Center, Netherlands

Publication history

  1. Received: June 9, 2016
  2. Accepted: October 1, 2016
  3. Accepted Manuscript published: October 5, 2016 (version 1)
  4. Version of Record published: October 14, 2016 (version 2)

Copyright

© 2016, Rose et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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