Identification of novel regulators of the long interspersed nuclear element-1 retrotransposon in humans
Abstract/Contents
- Abstract
- First identified by Barbara McClintock in Zea mays, transposable elements are now recognized not only as parasitic DNA, the spread of which in the genome must be controlled by the host, but also as major players in genome evolution and regulation. The most abundant and only currently autonomously active transposable element in the human genome, LINE-1, contributes to inter- and intragenic variation within the human population. In addition, LINE-1 sequences can regulate transcriptional programs in cis and trans as well as lead to the mobilization of other cellular mRNAs, including other transposons. Here I address how cells defend against LINE-1 mobile activity, as well as explore the extent to which LINE-1 sequences are transcribed in adult human somatic tissues. Chapter 1 provides a short historical introduction to the identification of transposable elements and the biology of the LINE-1 transposon. In chapter 2, I describe our high-throughput screening approaches to identify key regulators of LINE-1 transposition. In addition to classifying regulators as acting through sequence dependent or independent mechanisms, we also identify the HUSH complex as a major regulator of LINE-1 activity in human cancer cells. In chapter 3, I use adult somatic tissue expression measurements from GTEx consortium to identify and describe somatic LINE-1 expression. We find tissue specific L1 expression, and further leverage publicly available ENCODE data to identify potential regulators of L1 transcription. In chapter 4 I discuss our findings from our screen and tissue-level expression analysis, with a focus on remaining unanswered questions. Taken together, these chapters improve our understanding host/LINE-1 interactions in human cells and tissues.
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 | 2018; ©2018 |
| Publication date | 2018; 2018 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Lee, Cameron Howard |
|---|---|
| Degree supervisor | Bassik, Michael |
| Thesis advisor | Bassik, Michael |
| Thesis advisor | Fire, Andrew Zachary |
| Thesis advisor | Villeneuve, Anne, 1959- |
| Degree committee member | Baker, Julie, (Professor of genetics) |
| Degree committee member | Fire, Andrew Zachary |
| Degree committee member | Villeneuve, Anne, 1959- |
| Associated with | Stanford University, Department of Genetics. |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Cameron Howard Lee. |
|---|---|
| Note | Submitted to the Department of Genetics. |
| Thesis | Thesis Ph.D. Stanford University 2018. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2018 by Cameron Lee
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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