Chromatin accessibility dynamics during C. elegans development reveal regulatory complexity and identify novel enhancers
Abstract/Contents
- Abstract
- Chromatin accessibility, a crucial component of genome regulation, has primarily been studied in homogenous and simple systems, such as isolated cell populations or early development models. Whether chromatin accessibility can be assessed in complex, dynamic systems in vivo with high sensitivity remains largely unexplored. In this study, I use ATAC-seq to identify chromatin accessibility changes in a whole animal, the model organism C. elegans, from embryogenesis to adulthood. Chromatin accessibility changes between developmental stages are highly reproducible, recapitulate histone modification changes, and reveal key regulatory aspects of the epigenomic landscape throughout organismal development. Further, chromatin accessibility measurements near transcription start sites are predictive of steady-state gene expression, and ATAC-seq dynamics are correlated with gene expression changes. Importantly, my analysis of dynamic changes in chromatin accessibility within whole organisms sensitively identified novel cell-type- and temporal-specific enhancers, which I functionally validate in vivo. Furthermore, by integrating transcription factor binding motifs into a machine learning framework, I identify EOR-1 as a potential early regulator of chromatin accessibility changes. My study provides a unique resource for C. elegans, a system in which the prevalence and importance of enhancers remains poorly characterized, and demonstrates the power of using whole organism chromatin accessibility to identify novel regulatory regions in complex systems.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2017 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Daugherty, Aaron Charles | |
|---|---|---|
| Associated with | Stanford University, Department of Genetics. | |
| Primary advisor | Brunet, Anne, 1972- | |
| Thesis advisor | Brunet, Anne, 1972- | |
| Thesis advisor | Fire, Andrew Zachary | |
| Thesis advisor | Kundaje, Anshul, 1980- | |
| Thesis advisor | Wysocka, Joanna, Ph. D | |
| Advisor | Fire, Andrew Zachary | |
| Advisor | Kundaje, Anshul, 1980- | |
| Advisor | Wysocka, Joanna, Ph. D |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Aaron Charles Daugherty. |
|---|---|
| Note | Submitted to the Department of Genetics. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2017. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2017 by Aaron Charles Daugherty
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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