Abstract

Eukaryotic genomes are organized dynamically through the repositioning of nucleosomes. Isw2 is an enzyme that has been previously defined as a genome-wide, non-specific nucleosome spacing factor. Here, we show that Isw2 instead acts as an obligately targeted nucleosome remodeler in vivo through physical interactions with sequence-specific factors. We demonstrate that Isw2- recruiting factors use small and previously uncharacterized epitopes, which direct Isw2 activity through highly conserved acidic residues in the Isw2 accessory protein Itc1. This interaction orients Isw2 on target nucleosomes, allowing for precise nucleosome positioning at targeted loci. Finally, we show that these critical acidic residues have been lost in the Drosophila lineage, potentially explaining the inconsistently characterized function of Isw2-like proteins. Altogether, these data suggest an 'interacting barrier model' where Isw2 interacts with a sequence-specific factor to accurately and reproducibly position a single, targeted nucleosome to define the precise border of phased chromatin arrays.

Data availability

Sequencing data have been deposited in GEO under accession code GSE149804

The following data sets were generated

Article and author information

Author details

  1. Drake A Donovan

    Institute of Molecular Biology, University of Oregon, Eugene, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Johnathan G Crandall

    Institute of Molecular Biology, University of Oregon, Eugene, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9144-3135
  3. Vi N Truong

    Institute of Molecular Biology, University of Oregon, Eugene, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Abigail L Vaaler

    Institute of Molecular Biology, University of Oregon, Eugene, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Thomas B Bailey

    Institute of Molecular Biology, University of Oregon, Eugene, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Devin Dinwiddie

    Institute of Molecular Biology, University of Oregon, Eugene, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Orion GB Banks

    Institute of Molecular Biology, University of Oregon, Eugene, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Laura E McKnight

    Institute of Molecular Biology, University of Oregon, Eugene, United States
    For correspondence
    lthom009@gmail.com
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4322-3066
  9. Jeffrey N McKnight

    Institute of Molecular Biology, University of Oregon, Eugene, United States
    Competing interests
    The authors declare that no competing interests exist.

Funding

National Institutes of Health (T32 GM007759)

  • Drake A Donovan
  • Orion GB Banks

National Institutes of Health (T32 GM007413)

  • Drake A Donovan
  • Vi N Truong

National Institute of General Medical Sciences (R01 GM129242)

  • Jeffrey N McKnight

Donald and Delia Baxter Foundation

  • Jeffrey N McKnight

Medical Research Foundation of Oregon

  • Jeffrey N McKnight

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

Reviewing Editor

  1. Jerry L Workman, Stowers Institute for Medical Research, United States

Version history

  1. Received: October 15, 2020
  2. Accepted: February 11, 2021
  3. Accepted Manuscript published: February 12, 2021 (version 1)
  4. Version of Record published: March 17, 2021 (version 2)

Copyright

© 2021, Donovan 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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  1. Drake A Donovan
  2. Johnathan G Crandall
  3. Vi N Truong
  4. Abigail L Vaaler
  5. Thomas B Bailey
  6. Devin Dinwiddie
  7. Orion GB Banks
  8. Laura E McKnight
  9. Jeffrey N McKnight
(2021)
Basis of specificity for a conserved and promiscuous chromatin remodeling protein
eLife 10:e64061.
https://doi.org/10.7554/eLife.64061

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https://doi.org/10.7554/eLife.64061

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    Funding:

    This work was supported by the Weizmann Krenter Foundation and the Weizmann – Ichilov (Tel Aviv Sourasky Medical Center) Collaborative Grant in Biomedical Research, by the Minerva Foundation, by the ISF KillCorona grant 3777/19.