Live imaging and biophysical modeling support a button-based mechanism of somatic homolog pairing in Drosophila
- University of California at Berkeley, United States
- Bowdoin College, United States
- Grenoble Alpes University, France
- University of California, Berkeley, United States
- 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
Myron Barber Child VI
Nicholas C Lammers
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.
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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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
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