X-chromosome target specificity diverged between dosage compensation mechanisms of two closely related Caenorhabditis species

  1. Qiming Yang
  2. Te-Wen Lo
  3. Katjuša Brejc
  4. Caitlin Schartner
  5. Edward J Ralston
  6. Denise M Lapidus
  7. Barbara J Meyer  Is a corresponding author
  1. Howard Hughes Medical Institute, University of California, Berkeley, United States
  2. Ithaca College, United States

Abstract

An evolutionary perspective enhances our understanding of biological mechanisms. Comparison of sex determination and X-chromosome dosage compensation mechanisms between the closely related nematode species C. briggsae (Cbr) and C. elegans (Cel) revealed that the genetic regulatory hierarchy controlling both processes is conserved, but the X-chromosome target specificity and mode of binding for the specialized condensin dosage compensation complex (DCC) controlling X expression have diverged. We identified two motifs within Cbr DCC recruitment sites that are highly enriched on X: 13-bp MEX and 30-bp MEX II. Mutating either MEX or MEX II in an endogenous recruitment site with multiple copies of one or both motifs reduced binding, but only removing all motifs eliminated binding in vivo. Hence, DCC binding to Cbr recruitment sites appears additive. In contrast, DCC binding to Cel recruitment sites is synergistic: mutating even one motif in vivo eliminated binding. Although all X-chromosome motifs share the sequence CAGGG, they have otherwise diverged so that a motif from one species cannot function in the other. Functional divergence was demonstrated in vivo and in vitro. A single nucleotide position in Cbr MEX can determine whether Cel DCC binds. This rapid divergence of DCC target specificity could have been an important factor in establishing reproductive isolation between nematode species and contrasts dramatically with conservation of target specificity for X-chromosome dosage compensation across Drosophila species and for transcription factors controlling developmental processes such as body-plan specification from fruit flies to mice.

Data availability

GEO GSE214714 is the accession number for the ChIP-seq data reported in this manuscript.

The following data sets were generated

Article and author information

Author details

  1. Qiming Yang

    Department of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, United States
    Competing interests
    No competing interests declared.
  2. Te-Wen Lo

    Department of Biology, Ithaca College, Ithaca, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1231-5531
  3. Katjuša Brejc

    Department of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4562-6109
  4. Caitlin Schartner

    Department of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, United States
    Competing interests
    Caitlin Schartner, Caitlin Schartner is affiliated with Roche Diagnostics. The author has no financial interests to declare..
  5. Edward J Ralston

    Department of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, United States
    Competing interests
    No competing interests declared.
  6. Denise M Lapidus

    Department of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, United States
    Competing interests
    No competing interests declared.
  7. Barbara J Meyer

    Department of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, United States
    For correspondence
    bjmeyer@berkeley.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6530-4588

Funding

Howard Hughes Medical Institute

  • Barbara J Meyer

National Institutes of Health (R35 GM131845)

  • Barbara J Meyer

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

Reviewing Editor

  1. Luisa Cochella, Johns Hopkins University School of Medicine, United States

Version history

  1. Preprint posted: December 5, 2022 (view preprint)
  2. Received: December 7, 2022
  3. Accepted: March 21, 2023
  4. Accepted Manuscript published: March 23, 2023 (version 1)
  5. Version of Record published: April 5, 2023 (version 2)

Copyright

© 2023, Yang 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. Qiming Yang
  2. Te-Wen Lo
  3. Katjuša Brejc
  4. Caitlin Schartner
  5. Edward J Ralston
  6. Denise M Lapidus
  7. Barbara J Meyer
(2023)
X-chromosome target specificity diverged between dosage compensation mechanisms of two closely related Caenorhabditis species
eLife 12:e85413.
https://doi.org/10.7554/eLife.85413

Share this article

https://doi.org/10.7554/eLife.85413

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