Physical Modeling of Chromatin with Heterogeneous Nucleosome Spacings
Abstract/Contents
- Abstract
- The spatial organization of chromatin — genomic DNA and its associated proteins — underpins key biological processes from controlling gene expression to facilitating DNA damage repair. At the most basic level of organization, 147bp segments of DNA wrap histone proteins to form nucleosomes, which create heterogeneously spaced kinks in an otherwise semiflexible double-helix. This geometrical effect has not previously been included in analytical treatments of chromosomal DNA. As a result, the relative contributions of this structural heterogeneity and the thermal fluctuations in the DNA on chromatin organization is currently unknown. To address this gap, we present an analytical model of chromatin, treating nucleosomes as arbitrarily spaced, rigid kinks, in a wormlike chain backbone. We demonstrate that changing the positions of nucleosomes between two genomic loci can affect their probability of contact by up to six orders of magnitude. We also show that averaging over these heterogeneous binding configurations leads to chromatin tracing out an effective wormlike chain that is drastically more elastic than bare DNA. Since chromatin must bend back on itself in order for enhancers to bind their targets, this change in elasticity has a profound influence on transcriptional regulation. In particular, we examine the effects of nucleosome positioning around gene promoters on the spreading of epigenetic modifications through transient chromatin looping. Collectively, our work demonstrates that heterogeneity in nucleosome spacing dominates both local and global chromatin organization.
Description
| Type of resource | text |
|---|---|
| Date created | May 20, 2019 |
Creators/Contributors
| Author | Kannan, Deepti |
|---|---|
| Primary advisor | Spakowitz, Andrew J. |
| Advisor | Das, Rhiju |
| Degree granting institution | Stanford University, Program in Engineering Physics |
Subjects
| Subject | biophysics |
|---|---|
| Subject | chromatin |
| Subject | DNA |
| Subject | polymer physics |
| Subject | epigenetics |
| Genre | Thesis |
Bibliographic information
| Related Publication |
B. Beltran*, D. Kannan*, Q. MacPherson, and A. J. Spakowitz. Heterogeneity in nucleosome spacing governs chromatin elasticity. Physical Review Letters. (In Review).
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| Related item | |
| Location | https://purl.stanford.edu/fq175hg9693 |
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- Use and reproduction
- User agrees that, where applicable, content will not be used to identify or to otherwise infringe the privacy or confidentiality rights of individuals. Content distributed via the Stanford Digital Repository may be subject to additional license and use restrictions applied by the depositor.
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
Preferred citation
- Preferred Citation
- Kannan, Deepti. (2019). Physical Modeling of Chromatin with Heterogeneous Nucleosome Spacings. Stanford Digital Repository. Available at: https://purl.stanford.edu/fq175hg9693
Collection
Undergraduate Theses, Program in Engineering Physics
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- Contact
- dkannan@stanford.edu
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