Chromatin and transcriptional regulation of cell identity and aging
Abstract/Contents
- Abstract
- The mechanisms that specify and ensure the stability of cellular identity throughout organismal lifespan are not entirely clear. In this work, I examine how chromatin signatures- in particular the breath of histone marks in the genome- may encode important biological information. Using adult neural progenitors (NPCs) as a model system, I have characterized one such signature, extensive regions of the active histone mark H3K4me3 or 'broad H3K4me3 domains.' We show that this signature marks different but specific sets of genes in different tissues and may therefore be used to find new genes with relevance to the cell type of interest. In neural progenitors, I have identified several of such genes, including the putative signaling protein FAM72A and the uncharacterized protein BAHCC1, which regulate neural progenitor neurogenesis and proliferation. Using machine learning and metanalysis of public data, we demonstrate that H3K4me3 breath correlates with unique regulation of RNA Polymerase II (PolII). There is both more paused PolII at the promoters of broad H3K4me3 marked genes and more elongating PolII across their gene bodies, suggesting a distinct transcriptional output. Indeed, we show that H3K4me3 breadth correlates with increased transcriptional consistency (i.e. low cell to cell or sample to sample variation). Finally, I demonstrate that in NPC cultures, as well as in public data of aging adult stem cells, H3K4me3 breadth is generally constant with aging. However, remodeling occurs at select genes, which may contribute to a loss of transcriptional control in some aging tissues. These studies may help inform our understanding of how chromatin controls transcriptional variation, particularly at cell specific regulatory genes, and how this variation could influence cellular function with aging or disease.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2015 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Pollina, Elizabeth Ann |
|---|---|
| Associated with | Stanford University, Cancer Biology Program. |
| Primary advisor | Brunet, Anne, 1972- |
| Thesis advisor | Brunet, Anne, 1972- |
| Thesis advisor | Bassik, Michael |
| Thesis advisor | Palmer, Theo |
| Thesis advisor | Rando, Thomas A |
| Advisor | Bassik, Michael |
| Advisor | Palmer, Theo |
| Advisor | Rando, Thomas A |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Elizabeth Ann Pollina. |
|---|---|
| Note | Submitted to the Program in Cancer Biology. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2015. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2015 by Elizabeth Ann Pollina
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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