Coarse-grained chromatin models for meiotic homolog pairing
Abstract/Contents
- Abstract
- The process of homolog recombination in Prophase I is a key step in sexual reproduction, and errors in this process can lead to chromosome nondisjunction and are a major contributor to birth defects. However, while we know that pairing involves the coordination of many independent loci on each chromosome, the mechanism by which these loci are robustly brought together is still unknown. While the polymer physics of bare DNA is well described by the wormlike chain model, Eukaryotic chromatin is far from bare, and the presence of histones, transcription factors and other proteins that drastically alter the structure of chromatin are likely to have a profound effect on the polymer physics of chromatin in early meiosis. Therefore, in order to compare in vivo data of homolog pairing dynamics to an analytical theory, we develop a theory for kinked wormlike chains, to incorporate the geometric effects of, for example, nucleosomes on the polymer physics of chromatin. We show that there exists an "effective" wormlike chain (with a rescaled persistence length) that describes the mesoscopic structure of nucleosome-laden chromatin. Using a novel statistical method for analyzing Markov renewal processes in finite time windows, we then compare trajectories of individual homologous loci during early meiosis in S. cerevisiae to our expectations based on first-principles polymer theory, using both analytical and simulation results. We show that homologous locus pairing is largely a transient process, and that no active forces bringing together the loci to reproduce our experimental data. This is consistent with homolog pairing being a purely thermally-driven process, despite its importance to the successful completion of meiosis. Further, our model demonstrates that it only takes a handful of homologous linkages per chromosome to reproduce the physics of fully "paired" chromosomes, illustrating how a single tethered locus can drastically restrict the diffusion of DNA tens to hundreds of kilobases away.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2021; ©2021 |
| Publication date | 2021; 2021 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Beltran, Bruno Gabriel |
|---|---|
| Degree supervisor | Spakowitz, Andrew James |
| Thesis advisor | Spakowitz, Andrew James |
| Thesis advisor | Boettiger, Alistair |
| Thesis advisor | Bryant, Zev David |
| Thesis advisor | Qin, Jian, (Professor of Chemical Engineering) |
| Degree committee member | Boettiger, Alistair |
| Degree committee member | Bryant, Zev David |
| Degree committee member | Qin, Jian, (Professor of Chemical Engineering) |
| Associated with | Stanford University, Biophysics Program |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Bruno Gabriel Beltran. |
|---|---|
| Note | Submitted to the Biophysics Program. |
| Thesis | Thesis Ph.D. Stanford University 2021. |
| Location | https://purl.stanford.edu/qc603tq9656 |
Access conditions
- Copyright
- © 2021 by Bruno Gabriel Beltran
- License
- This work is licensed under a Creative Commons Attribution Share Alike 3.0 Unported license (CC BY-SA).
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