1. Chromosomes and Gene Expression
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The conformation of the histone H3 tail inhibits association of the BPTF PHD finger with the nucleosome

  1. Emma A Morrison
  2. Samuel Bowerman
  3. Kelli L Sylvers
  4. Jeff Wereszczynski  Is a corresponding author
  5. Catherine A Musselman  Is a corresponding author
  1. University of Iowa, United States
  2. Illinois Institute of Technology, United States
Research Article
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Cite as: eLife 2018;7:e31481 doi: 10.7554/eLife.31481

Abstract

Histone tails harbor a plethora of post-translational modifications that direct the function of chromatin regulators, which recognize them through effector domains. Effector domain/histone interactions have been broadly studied, but largely using peptide fragments of histone tails. Here, we extend these studies into the nucleosome context and find that the conformation adopted by the histone H3 tails is inhibitory to BPTF PHD finger binding. Using NMR spectroscopy and MD simulations, we show that the H3 tails interact robustly but dynamically with nucleosomal DNA, substantially reducing PHD finger association. Altering the electrostatics of the H3 tail via modification or mutation increases accessibility to the PHD finger, indicating that PTM crosstalk can regulate effector domain binding by altering nucleosome conformation. Together, our results demonstrate that the nucleosome context has a dramatic impact on signaling events at the histone tails, and highlights the importance of studying histone binding in the context of the nucleosome.

Article and author information

Author details

  1. Emma A Morrison

    Department of Biochemistry, University of Iowa, Iowa City, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon 0000-0001-6722-7961
  2. Samuel Bowerman

    Department of Physics, Illinois Institute of Technology, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon 0000-0003-0753-4294
  3. Kelli L Sylvers

    Department of Biochemistry, University of Iowa, Iowa City, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon 0000-0003-0711-402X
  4. Jeff Wereszczynski

    Department of Physics, Illinois Institute of Technology, Chicago, United States
    For correspondence
    jwereszc@iit.edu
    Competing interests
    The authors declare that no competing interests exist.
  5. Catherine A Musselman

    Department of Biochemistry, University of Iowa, Iowa City, United States
    For correspondence
    catherine-musselman@uiowa.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon 0000-0002-8356-7971

Funding

National Science Foundation (1452411)

  • Catherine A Musselman

National Science Foundation (1552743)

  • Samuel Bowerman
  • Jeff Wereszczynski

Arnold and Mabel Beckman Foundation (Postdoctoral Fellowship)

  • Emma A Morrison

National Institutes of Health (R35GM119647)

  • Jeff Wereszczynski

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, Reviewing Editor, University of California, San Francisco, United States

Publication history

  1. Received: August 23, 2017
  2. Accepted: April 11, 2018
  3. Accepted Manuscript published: April 12, 2018 (version 1)

Copyright

© 2018, Morrison 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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