1. Biochemistry and Chemical Biology
  2. Chromosomes and Gene Expression
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Specialization of the chromatin remodeler RSC to mobilize partially-unwrapped nucleosomes

  1. Alisha Schlichter
  2. Margaret M Kasten
  3. Timothy J Parnell
  4. Bradley R Cairns  Is a corresponding author
  1. Howard Hughes Medical Institute, University of Utah School of Medicine, United States
Research Article
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Cite this article as: eLife 2020;9:e58130 doi: 10.7554/eLife.58130

Abstract

SWI/SNF-family chromatin remodeling complexes, such as S. cerevisiae RSC, slide and eject nucleosomes to regulate transcription. Within nucleosomes, stiff DNA sequences confer spontaneous partial unwrapping, prompting whether and how SWI/SNF-family remodelers are specialized to remodel partially-unwrapped nucleosomes. RSC1 and RSC2 are orthologs of mammalian PBRM1 (polybromo) which define two separate RSC sub-complexes. Remarkably, in vitro the Rsc1-containing complex remodels partially-unwrapped nucleosomes much better than does the Rsc2-containing complex. Moreover, a rsc1Δ mutation, but not rsc2Δ, is lethal with histone mutations that confer partial unwrapping. Rsc1/2 isoforms both cooperate with the DNA-binding proteins Rsc3/30 and the HMG protein, Hmo1, to remodel partially-unwrapped nucleosomes, but show differential reliance on these factors. Notably, genetic impairment of these factors strongly reduces the expression of genes with wide nucleosome-deficient regions (e.g. ribosomal protein genes), known to harbor partially-unwrapped nucleosomes. Taken together, Rsc1/2 isoforms are specialized through composition and interactions to manage and remodel partially-unwrapped nucleosomes.

Data availability

Data Availability: Sequencing data has been deposited at NCBI under SRA accession #PRJNA573112. Source data files have been provided for Figures 3, 4, and 5.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Alisha Schlichter

    Department of Oncological Sciences, Howard Hughes Medical Institute, University of Utah School of Medicine, Salt Lake City, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1928-9396
  2. Margaret M Kasten

    Department of Oncological Sciences, Howard Hughes Medical Institute, University of Utah School of Medicine, Salt Lake City, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Timothy J Parnell

    Department of Radiation Oncology and Huntsman Cancer Institute, Howard Hughes Medical Institute, University of Utah School of Medicine, Salt Lake City, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3632-3691
  4. Bradley R Cairns

    Department of Oncological Sciences, Howard Hughes Medical Institute, University of Utah School of Medicine, Salt Lake City, United States
    For correspondence
    brad.cairns@hci.utah.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9864-8811

Funding

Howard Hughes Medical Institute (Brad Cairns Investigator)

  • Alisha Schlichter
  • Margaret M Kasten
  • Bradley R Cairns

National Cancer Institute (CA042014)

  • Timothy J Parnell

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

Reviewing Editor

  1. Stephen Buratowski, Harvard Medical School, United States

Publication history

  1. Received: April 22, 2020
  2. Accepted: June 3, 2020
  3. Accepted Manuscript published: June 4, 2020 (version 1)
  4. Version of Record published: June 22, 2020 (version 2)

Copyright

© 2020, Schlichter 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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