Using chromatin dynamics to understand transcriptional regulation and genetic variance

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Abstract/Contents

Abstract
The genome is the same in every cell of an organism, but complex organisms have multiple cell types. This is due to the epigenome specifying a cell's transcriptional state resulting in distinct cell identities. Despite 98.5% of the human genome is non-coding and the site of epigenomic activity, which specifies instructions for regulating transcription of the coding region, relatively little is known about its function. A major hurdle with studying non-coding regulatory elements is identifying their distal gene and regulatory targets. Here, I solve this issue by using the three-dimensional chromatin conformation to identify targets that are in close physical proximity of the regulatory element. By integrating data on the three-dimensional chromatin state with other epigenomic measures including the open chromatin regions, transcription factor binding sites, and histone modifications I provide genome-wide insight into how the epigenome establishes the transcriptional state of the cell. In addition, I have developed a new method for prioritizing non-coding genetic variants in complex phenotypes. I validated this method in the context of Type 1 Diabetes and craniofacial disorders. In this dissertation, I demonstrate how data integration of multiple measurements of the epigenome and transcriptome provides insight into methods of transcriptional regulation and how this regulation is influenced by genetic variance.

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 2020; ©2020
Publication date 2020; 2020
Issuance monographic
Language English

Creators/Contributors

Author Piekos, Samantha Nicole
Degree supervisor Oro, Anthony, 1958-
Thesis advisor Oro, Anthony, 1958-
Thesis advisor Greenleaf, William James
Thesis advisor Wernig, Marius
Thesis advisor Wysocka, Joanna, Ph. D.
Degree committee member Greenleaf, William James
Degree committee member Wernig, Marius
Degree committee member Wysocka, Joanna, Ph. D.
Associated with Stanford University, Department of Stem Cell Biology and Regenerative Medicine

Subjects

Genre Theses
Genre Text

Bibliographic information

Statement of responsibility Samantha Nicole Piekos.
Note Submitted to the Department of Stem Cell Biology and Regenerative Medicine.
Thesis Thesis Ph.D. Stanford University 2020.
Location electronic resource

Access conditions

Copyright
© 2020 by Samantha Nicole Piekos
License
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

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