Live imaging and biophysical modeling support a button-based mechanism of somatic homolog pairing in Drosophila

  1. Myron Barber Child VI
  2. Jack R Bateman  Is a corresponding author
  3. Amir Jahangiri
  4. Armando Reimer
  5. Nicholas C Lammers
  6. Nica Sabouni
  7. Diego Villamarin
  8. Grace C McKenzie-Smith
  9. Justine E Johnson
  10. Daniel Jost  Is a corresponding author
  11. Hernan G Garcia  Is a corresponding author
  1. University of California at Berkeley, United States
  2. Bowdoin College, United States
  3. Grenoble Alpes University, France
  4. University of California, Berkeley, United States
  5. ENS de Lyon, France

Abstract

3D eukaryotic genome organization provides the structural basis for gene regulation. In Drosophila melanogaster, genome folding is characterized by somatic homolog pairing, where homologous chromosomes are intimately paired from end to end; however, how homologs identify one another and pair has remained mysterious. Recently, this process has been proposed to be driven by specifically interacting 'buttons' encoded along chromosomes. Here, we turned this hypothesis into a quantitative biophysical model to demonstrate that a button-based mechanism can lead to chromosome-wide pairing. We tested our model using live-imaging measurements of chromosomal loci tagged with the MS2 and PP7 nascent RNA labeling systems. We show solid agreement between model predictions and experiments in the pairing dynamics of individual homologous loci. Our results strongly support a button-based mechanism of somatic homolog pairing in Drosophila and provide a theoretical framework for revealing the molecular identity and regulation of buttons.

Data availability

Modeling code is available at: https://github.com/physical-biology-of-chromatin/Homologous_pairingCustom Matlab 2019b image analysis scripts can be found at https://github.com/GarciaLab/mRNADynamics/.Raw figure files of relevant plots are available at: https://www.dropbox.com/sh/cwe1t3u5q4v3yos/AACTXXBF6WiOuLuozX0MZRkba?dl=0Samples of generated data used in this study are included in the manuscript and supporting files

Article and author information

Author details

  1. Myron Barber Child VI

    Molecular and Cell Biology, University of California at Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8563-0842
  2. Jack R Bateman

    Biology, Bowdoin College, Brunswick, United States
    For correspondence
    jbateman@bowdoin.edu
    Competing interests
    The authors declare that no competing interests exist.
  3. Amir Jahangiri

    TIMC-IMAG, Grenoble Alpes University, La Tronche, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Armando Reimer

    Biophysics Graduate Group, University of California, Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Nicholas C Lammers

    Biophysics Graduate Group, University of California, Berkeley, Oakland, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6832-6152
  6. Nica Sabouni

    Molecular and Cell Biology, University of California at Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Diego Villamarin

    Biology, Bowdoin College, Brunswick, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3265-1740
  8. Grace C McKenzie-Smith

    Biology, Bowdoin College, Brunswick, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Justine E Johnson

    Biology, Bowdoin College, Brunswick, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Daniel Jost

    Laboratory of Biology and Modelling of the Cell, ENS de Lyon, Lyon, France
    For correspondence
    daniel.jost@ens-lyon.fr
    Competing interests
    The authors declare that no competing interests exist.
  11. Hernan G Garcia

    Molecular and Cell Biology, Physics, University of California, Berkeley, Berkeley, United States
    For correspondence
    hggarcia@berkeley.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5212-3649

Funding

Burroughs Wellcome Fund (Career Award at the Scientific Interface)

  • Hernan G Garcia

ITMO Cancer (BIO2015-08)

  • Daniel Jost

National Institutes of Health (P20 GM0103423,R15 GM132896-01)

  • Jack R Bateman

National Science Foundation (CAREER Award 1349779)

  • Jack R Bateman

Alfred P. Sloan Foundation (Sloan Research Fellowship)

  • Hernan G Garcia

Human Frontier Science Program

  • Hernan G Garcia

Searle Scholars Program

  • Hernan G Garcia

Shurl and Kay Curci Foundation

  • Hernan G Garcia

Hellman Foundation

  • Hernan G Garcia

National Institutes of Health (Director's New Innovator Award,DP2 OD024541-01)

  • Hernan G Garcia

National Science Foundation (CAREER Award,1652236)

  • Hernan G Garcia

Agence Nationale pour la Recherche (ANR-18-CE12-0006-03,ANR-18-CE45-0022-01)

  • Daniel Jost

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

Reviewing Editor

  1. Pierre Sens, Institut Curie, PSL Research University, CNRS, France

Version history

  1. Received: October 28, 2020
  2. Accepted: June 7, 2021
  3. Accepted Manuscript published: June 8, 2021 (version 1)
  4. Version of Record published: July 21, 2021 (version 2)

Copyright

© 2021, Child 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. Myron Barber Child VI
  2. Jack R Bateman
  3. Amir Jahangiri
  4. Armando Reimer
  5. Nicholas C Lammers
  6. Nica Sabouni
  7. Diego Villamarin
  8. Grace C McKenzie-Smith
  9. Justine E Johnson
  10. Daniel Jost
  11. Hernan G Garcia
(2021)
Live imaging and biophysical modeling support a button-based mechanism of somatic homolog pairing in Drosophila
eLife 10:e64412.
https://doi.org/10.7554/eLife.64412

Share this article

https://doi.org/10.7554/eLife.64412

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