Live imaging and biophysical modeling support a button-based mechanism of somatic homolog pairing in Drosophila
Citation
Child, Myron Barber et al. (2021), Live imaging and biophysical modeling support a button-based mechanism of somatic homolog pairing in Drosophila, Dryad, Dataset, https://doi.org/10.5061/dryad.3j9kd51j5
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.
Funding
Burroughs Wellcome Fund, Award: Career Award at the Scientific Interface
National Institutes of Health, Award: P20 GM0103423
National Institutes of Health, Award: Director's New Innovator Award DP2 OD024541-01
National Science Foundation, Award: CAREER Award 652236
National Science Foundation, Award: CAREER Award 1349779
Alfred P. Sloan Foundation, Award: Sloan Research Fellowship
Searle Scholars Program
Shurl and Kay Curci Foundation
Hellman Foundation
ITMO Cancer, Award: BIO2015-08
Human Frontier Science Program
Agence Nationale pour le Développement de la Recherche Universitaire, Award: ANR-18-CE12-0006-03
National Institutes of Health, Award: R15 GM132896-01
National Institutes of Health
Agence Nationale pour le Développement de la Recherche Universitaire, Award: ANR-18-CE45-0022-01