1. Biochemistry and Chemical Biology
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Diverse nucleosome site-selectivity among histone deacetylase complexes

  1. Zhipeng A Wang
  2. Christopher J Millard
  3. Chia-Liang Lin
  4. Jennifer E Gurnett
  5. Mingxuan Wu
  6. Kwangwoon Lee
  7. Louise Fairall
  8. John W R Schwabe  Is a corresponding author
  9. Philip A Cole  Is a corresponding author
  1. Brigham and Women's Hospital, United States
  2. University of Leicester, United Kingdom
  3. Harvard Medical School, United States
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Cite this article as: eLife 2020;9:e57663 doi: 10.7554/eLife.57663

Abstract

Histone acetylation regulates chromatin structure and gene expression and is removed by histone deacetylases (HDACs). HDACs are commonly found in various protein complexes to confer distinct cellular functions, but how the multi-subunit complexes influence deacetylase activities and site-selectivities in chromatin is poorly understood. Previously we reported the results of studies on the HDAC1 containing CoREST complex and acetylated nucleosome substrates which revealed a notable preference for deacetylation of histone H3 acetyl-Lys9 vs. acetyl-Lys14 (M. Wu et al, 2018). Here we analyze the enzymatic properties of five class I HDAC complexes: CoREST, NuRD, Sin3B, MiDAC and SMRT with site-specific acetylated nucleosome substrates. Our results demonstrate that these HDAC complexes show a wide variety of deacetylase rates in a site-selective manner. A Gly13 in the histone H3 tail is responsible for a sharp reduction in deacetylase activity of the CoREST complex for H3K14ac. These studies provide a framework for connecting enzymatic and biological functions of specific HDAC complexes.

Data availability

Data has been uploaded to Dryad under the doi:10.5061/dryad.x0k6djhgc

The following data sets were generated

Article and author information

Author details

  1. Zhipeng A Wang

    Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5693-7359
  2. Christopher J Millard

    Leicester Institute of Structural and Chemical Biology, Department of Molecular and Cell Biology, University of Leicester, Leicester, United Kingdom
    Competing interests
    No competing interests declared.
  3. Chia-Liang Lin

    Leicester Institute of Structural and Chemical Biology, Department of Molecular and Cell Biology, University of Leicester, Leicester, United Kingdom
    Competing interests
    No competing interests declared.
  4. Jennifer E Gurnett

    Leicester Institute of Structural and Chemical Biology, Department of Molecular and Cell Biology, University of Leicester, Leicester, United Kingdom
    Competing interests
    No competing interests declared.
  5. Mingxuan Wu

    Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, United States
    Competing interests
    No competing interests declared.
  6. Kwangwoon Lee

    Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, United States
    Competing interests
    No competing interests declared.
  7. Louise Fairall

    Leicester Institute of Structural and Chemical Biology, Department of Molecular and Cell Biology, University of Leicester, Leicester, United Kingdom
    Competing interests
    No competing interests declared.
  8. John W R Schwabe

    Leicester Institute of Structural and Chemical Biology, Department of Molecular and Cell Biology, University of Leicester, Leicester, United Kingdom
    For correspondence
    john.schwabe@le.ac.uk
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2865-4383
  9. Philip A Cole

    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, United States
    For correspondence
    pacole@bwh.harvard.edu
    Competing interests
    Philip A Cole, Senior editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6873-7824

Funding

NIH (GM62437)

  • Philip A Cole

Leukemia and Lymphoma Society (SCOR)

  • Philip A Cole

Wellcome Trust Senior Investigator Award (100237/Z/12/Z)

  • John W R Schwabe

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

Reviewing Editor

  1. Wilfred A van der Donk, University of Illinois at Urbana-Champaign, United States

Publication history

  1. Received: April 9, 2020
  2. Accepted: June 4, 2020
  3. Accepted Manuscript published: June 5, 2020 (version 1)
  4. Version of Record published: June 25, 2020 (version 2)

Copyright

© 2020, Wang 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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