A novel chromatin opening element for resisting transgene silencing in mammalian cells
Abstract/Contents
- Abstract
- Long-term stable expression of transgenes in mammalian cells is important in gene therapy, recombinant protein production, genetic reprogramming and mammalian synthetic biology. However, transgenes are susceptible to time-dependent epigenetic silencing, as well as position effect variegation, making reproducible stable expression challenging. To counteract this problem, genetic engineers have discovered and characterized various chromatin insulator sequences that promote consistent long-term expression; however, these elements are also often cumbersome to use due to length and copy requirements, and have varying effect depending on cell type and genetic context. A more recent development in the field was the discovery and validation of a Ubiquitous Chromatin Opening Element (UCOE), a sequence from the human genome, which drastically outperforms traditional chromatin insulators due to its activating features. In order to discover more UCOEs, we developed a bioinformatics algorithm based on the epigenetic features of the published UCOE and screened the resulting candidates to discover a novel UCOE that is shorter in length and more modular. We show that our novel UCOE prevents time-dependent silencing and significantly stabilizes gene expression in a variety of genetic contexts.
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 | 2019; ©2019 |
| Publication date | 2019; 2019 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Rudina, Shireen S |
|---|---|
| Degree supervisor | Smolke, Christina D |
| Thesis advisor | Smolke, Christina D |
| Thesis advisor | Bintu, Lacramioara |
| Thesis advisor | Kay, Mark Allan |
| Degree committee member | Bintu, Lacramioara |
| Degree committee member | Kay, Mark Allan |
| Associated with | Stanford University, Department of Bioengineering. |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Shireen Rudina. |
|---|---|
| Note | Submitted to the Department of Bioengineering. |
| Thesis | Thesis Ph.D. Stanford University 2019. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2019 by Shireen S Rudina
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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