PT  - JOURNAL ARTICLE
AU  - Myron Child VI
AU  - Jack R. Bateman
AU  - Amir Jahangiri
AU  - Armando Reimer
AU  - Nicholas C. Lammers
AU  - Nica Sabouni
AU  - Diego Villamarin
AU  - Grace C. McKenzie-Smith
AU  - Justine E. Johnson
AU  - Daniel Jost
AU  - Hernan G. Garcia
TI  - Live imaging and biophysical modeling support a button-based mechanism of somatic homolog pairing in <em>Drosophila</em>
AID  - 10.1101/2020.08.30.265108
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.08.30.265108
4099  - http://biorxiv.org/content/early/2020/09/16/2020.08.30.265108.short
4100  - http://biorxiv.org/content/early/2020/09/16/2020.08.30.265108.full
AB  - The spatial configuration of the eukaryotic genome is organized and dynamic, providing the structural basis for regulated gene expression in living cells. In Drosophila melanogaster, 3D genome organization is characterized by somatic homolog pairing, where homologous chromosomes are intimately paired from end to end; however, the process by which homologs identify one another and pair has remained mysterious. A recent model proposed that specifically interacting “buttons” encoded along the lengths of homologous chromosomes drive somatic homolog pairing. Here, we turned this hypothesis into a precise biophysical model to demonstrate that a button-based mechanism can lead to chromosome-wide pairing. We tested our model and constrained its free parameters using live-imaging measurements of chromosomal loci tagged with the MS2 and PP7 nascent RNA labeling systems. Our analysis showed strong agreement between model predictions and experiments in the separation dynamics of tagged homologous loci as they transition from unpaired to paired states, and in the percentage of nuclei that become paired as embryonic development proceeds. In sum, as a result of this dialogue between theory and experiment, our data 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.Competing Interest StatementThe authors have declared no competing interest.