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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