1. Long-Range Structural Changes in the Meiotic Nucleus Revealed by Changes in Stress Communication Along the Chromosome
- Author
-
Daniel Elnatan, Cori K. Cahoon, Daniel B. Chu, Andrew J. Spakowitz, Sean M. Burgess, Bruno Beltran, James McGehee, and Trent Newman
- Subjects
Physics ,medicine.anatomical_structure ,Meiosis ,Pairing ,Biophysics ,Homologous chromosome ,medicine ,Chromosome ,Sister chromatids ,Homologous recombination ,Nucleus ,Chromatin - Abstract
Homologous recombination drives structural reorganization of the nucleus in early meiosis. In order to investigate the connection between homolog pairing, meiotic progression, and the dynamics of the underlying chromatin, we tracked flourescently labeled homolog pairs in synchronized S. cerevisae. Various previously unreported statistics of the anomalous inter-loci motion correlate with meiotic progression and can be quantitatively reproduced by a simple polymer model of the sister chromatids. The first of these is the distribution of waiting times for the homologous loci to come into and out of contact with each other (loosely, inter-locus “looping” and “unlooping” times). The full shape of the looping time distribution can be quantitatively reproduced by a simple model of two polymers diffusing independently in a spherical confinement. This finding suggests a dominant role for diffusion-limited, undirected search in homolog pairing in early meiosis. This is in sharp contrast with the intuition that a heavy-tailed search process could never drive such a critical cell-cycle stage. We further show that the inter-locus velocity-velocity correlation (VVC) quantitatively matches analytical results for the inter-locus VVC of our polymer model, allowing us to leverage our analytical theory to extract the time scale of stress communication between the labeled loci along the chromosome. We show that stresses can take tens of minutes to propagate between loci on paired chromosomes, and that the increasing connectivity between the chromosomes as the cell progresses through meiosis can be quantified by the shortening of this communication time. Our study highlights the power of coarse-grained polymer models to analyze dynamic structural properties of the nucleus in vivo and the importance of analytical theory for uncovering intracellular connections that might be obscured by lag times of many minutes.
- Published
- 2018
- Full Text
- View/download PDF