1. Chromosomes and Gene Expression
  2. Genetics and Genomics
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A combination of transcription factors mediates inducible interchromosomal contacts

  1. Seungsoo Kim
  2. Maitreya J Dunham
  3. Jay Shendure  Is a corresponding author
  1. University of Washington, United States
Research Article
  • Cited 5
  • Views 3,660
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Cite this article as: eLife 2019;8:e42499 doi: 10.7554/eLife.42499

Abstract

The genome forms specific three-dimensional contacts in response to cellular or environmental conditions. However, it remains largely unknown which proteins specify and mediate such contacts. Here we describe an assay, MAP-C (Mutation Analysis in Pools by Chromosome conformation capture), that simultaneously characterizes the effects of hundreds of cis or trans-acting mutations on a chromosomal contact. Using MAP-C, we show that inducible interchromosomal pairing between HAS1pr-TDA1pr alleles in saturated cultures of Saccharomyces yeast is mediated by three transcription factors, Leu3, Sdd4 (Ypr022c), and Rgt1. The coincident, combined binding of all three factors is strongest at the HAS1pr-TDA1pr locus and is also specific to saturated conditions. We applied MAP-C to further explore the biochemical mechanism of these contacts, and find they require the structured regulatory domain of Rgt1, but no known interaction partners of Rgt1. Altogether, our results demonstrate MAP-C as a powerful method for dissecting the mechanistic basis of chromosome conformation.

Article and author information

Author details

  1. Seungsoo Kim

    Department of Genome Sciences, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5559-5289
  2. Maitreya J Dunham

    Department of Genome Sciences, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9944-2666
  3. Jay Shendure

    Department of Genome Sciences, University of Washington, Seattle, United States
    For correspondence
    shendure@uw.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1516-1865

Funding

National Institutes of Health (U54 DK107979)

  • Jay Shendure

National Science Foundation (Graduate Research Fellowship DGE-1256082)

  • Seungsoo Kim

Howard Hughes Medical Institute (Investigator)

  • Jay Shendure

Canadian Institute for Advanced Research (Senior Fellow (Genetic Networks Program))

  • Maitreya J Dunham

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

Reviewing Editor

  1. Jeannie T Lee, Massachusetts General Hospital, United States

Publication history

  1. Received: October 2, 2018
  2. Accepted: May 11, 2019
  3. Accepted Manuscript published: May 13, 2019 (version 1)
  4. Version of Record published: June 4, 2019 (version 2)

Copyright

© 2019, Kim 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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