1. Biochemistry and Chemical Biology
  2. Chromosomes and Gene Expression
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FACT and Ubp10 collaborate to modulate H2B deubiquitination and nucleosome dynamics

  1. Melesse Nune
  2. Michael T Morgan
  3. Zaily Connell
  4. Laura McCullough
  5. Muhammad Jbara
  6. Hao Sun
  7. Ashraf Brik
  8. Tim Formosa  Is a corresponding author
  9. Cynthia Wolberger  Is a corresponding author
  1. Johns Hopkins University School of Medicine, United States
  2. University of Utah School of Medicine, United States
  3. Technion-Israel Institute of Technology, Israel
Research Article
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Cite this article as: eLife 2019;8:e40988 doi: 10.7554/eLife.40988

Abstract

Monoubiquitination of histone H2B (H2B-Ub) plays a role in transcription and DNA replication, and is required for normal localization of the histone chaperone, FACT. In yeast, H2B-Ub is deubiquitinated by Ubp8, a subunit of SAGA, and Ubp10. Although they target the same substrate, loss of Ubp8 and Ubp10 cause different phenotypes and alter the transcription of different genes. We show that Ubp10 has poor activity on yeast nucleosomes, but that the addition of FACT stimulates Ubp10 activity on nucleosomes and not on other substrates. Consistent with a role for FACT in deubiquitinating H2B in vivo, a FACT mutant strain shows elevated levels of H2B-Ub. Combination of FACT mutants with deletion of Ubp10, but not Ubp8, confers increased sensitivity to hydroxyurea and activates a cryptic transcription reporter, suggesting that FACT and Ubp10 may coordinate nucleosome assembly during DNA replication and transcription. Our findings reveal unexpected interplay between H2B deubiquitination and nucleosome dynamics.

Article and author information

Author details

  1. Melesse Nune

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

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

    Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, United States
    Competing interests
    No competing interests declared.
  4. Laura McCullough

    Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, United States
    Competing interests
    No competing interests declared.
  5. Muhammad Jbara

    Schulich Faculty of Chemistry, Technion-Israel Institute of Technology, Haifa, Israel
    Competing interests
    No competing interests declared.
  6. Hao Sun

    Schulich Faculty of Chemistry, Technion-Israel Institute of Technology, Haifa, Israel
    Competing interests
    No competing interests declared.
  7. Ashraf Brik

    Schulich Faculty of Chemistry, Technion-Israel Institute of Technology, Haifa, Israel
    Competing interests
    No competing interests declared.
  8. Tim Formosa

    Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, United States
    For correspondence
    tim@biochem.utah.edu
    Competing interests
    Tim Formosa, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8477-2483
  9. Cynthia Wolberger

    Department of Biophysics and Biophysical Chemnistry, Johns Hopkins University School of Medicine, Baltimore, United States
    For correspondence
    cwolberg@jhmi.edu
    Competing interests
    Cynthia Wolberger, Reviewing editor, eLifeon the scientific advisory board of ThermoFisher Scientific.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8578-2969

Funding

National Institute of General Medical Sciences (GM095822)

  • Cynthia Wolberger

National Institute of General Medical Sciences (GM064649)

  • Tim Formosa

National Science Foundation (Graduate Research Fellowship)

  • Melesse Nune

Jordan and Irene Tark Academic Chair

  • Ashraf Brik

Israel Council of Higher Education (Fellowship)

  • Muhammad Jbara

National Institute of General Medical Sciences (Training Grant GM008403)

  • Melesse Nune

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

Reviewing Editor

  1. Geeta J Narlikar, University of California, San Francisco, United States

Publication history

  1. Received: August 10, 2018
  2. Accepted: January 24, 2019
  3. Accepted Manuscript published: January 25, 2019 (version 1)
  4. Version of Record published: February 12, 2019 (version 2)

Copyright

© 2019, Nune 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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