1. Chromosomes and Gene Expression
  2. Structural Biology and Molecular Biophysics
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Structural basis for COMPASS recognition of an H2B-ubiquitinated nucleosome

  1. Evan J Worden
  2. Xiangbin Zhang
  3. Cynthia Wolberger  Is a corresponding author
  1. Johns Hopkins University School of Medicine, United States
Research Article
  • Cited 22
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Cite this article as: eLife 2020;9:e53199 doi: 10.7554/eLife.53199


Methylation of histone H3K4 is a hallmark of actively transcribed genes that depends on mono-ubiquitination of histone H2B (H2B-Ub). H3K4 methylation in yeast is catalyzed by Set1, the methyltransferase subunit of COMPASS. We report here the cryo-EM structure of a six-protein core COMPASS subcomplex, which can methylate H3K4 and be stimulated by H2B-Ub, bound to a ubiquitinated nucleosome. Our structure shows that COMPASS spans the face of the nucleosome, recognizing ubiquitin on one face of the nucleosome and methylating H3 on the opposing face. As compared to the structure of the isolated core complex, Set1 undergoes multiple structural rearrangements to cement interactions with the nucleosome and with ubiquitin. The critical Set1 RxxxRR motif adopts a helix that mediates bridging contacts between the nucleosome, ubiquitin and COMPASS. The structure provides a framework for understanding mechanisms of trans-histone cross-talk and the dynamic role of H2B ubiquitination in stimulating histone methylation.

Article and author information

Author details

  1. Evan J Worden

    Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, United States
    Competing interests
    No competing interests declared.
  2. Xiangbin Zhang

    Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, United States
    Competing interests
    No competing interests declared.
  3. Cynthia Wolberger

    Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, United States
    For correspondence
    Competing interests
    Cynthia Wolberger, Senior editor, eLife; is a member of the scientific advisory board of ThermoFisher Scientific.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8578-2969


National Institute of General Medical Sciences (GM130393)

  • Cynthia Wolberger

Damon Runyon Cancer Research Foundation (DRG 2308-17)

  • Evan J Worden

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

Reviewing Editor

  1. John Kuriyan, University of California, Berkeley, United States

Publication history

  1. Received: October 31, 2019
  2. Accepted: January 10, 2020
  3. Accepted Manuscript published: January 10, 2020 (version 1)
  4. Version of Record published: February 24, 2020 (version 2)


© 2020, Worden 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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