Live imaging and biophysical modeling support a button-based mechanism of somatic homolog pairing in Drosophila
Year: 2021
Type: article
Abstract: 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.
Source: eLife
DOI: 10.7554/elife.64412
Institutions: University of California, Berkeley, Bowdoin College, Institut polytechnique de Grenoble, Centre National de la Recherche Scientifique, Translational Innovation in Medicine and Complexity, Université Grenoble Alpes, Lyon 1 Université, École Normale Supérieure de Lyon, Université de Lyon, Laboratoire de Biologie et Modélisation de la Cellule, QB3
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,500
Funders: National Science Foundation, Burroughs Wellcome Fund, Alfred P. Sloan Foundation, Shurl and Kay Curci Foundation, Hellman Foundation, Searle Scholars Program, Human Frontier Science Program, Agence Nationale de la Recherche, ITMO University, National Institutes of Health, National Human Genome Research Institute, National Institute of General Medical Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1079525982, G1723340172, G2239895548, G2430628023, G2673461945, Know your neighbors: investigating the influence of gene co-localization on transcriptional dynamics, G3679594321, CAREER: Predictive Understanding and Control of Embryonic Developmental Programs, CAREER: Mechanisms of cis-/trans-promoter competition in Drosophila, G462665505, G4656594441, G6063616604, G6671297155, Quantitative modeling of the 3D dynamical organization of chromosomes, Single gene Focus during Nuclear receptor Induced Expression : mechanisms of cellular differentiation
OpenAlex ID: W3168821798