Transcription factors regulate enhancer-promoter contact dynamics in differentiation and disease
Abstract/Contents
- Abstract
- Since the development of chromosome conformation capture (3C) by Job Dekker et al. in 2002, interrogation of enhancer-promoter interactions has led to an increased understanding of the vital role that three-dimensional structure plays in gene regulation. However, the technical difficulty of 3C and related assays, as well as the sequencing depth required to make quantitative comparisons between contact frequencies in HiC, have limited investigations of enhancer-promoter dynamics in differentiation and disease. Knowledge of the contact landscape is critical to our understanding of both human disease and normal tissue function. For example, the correlation of common genetic variation with associated diseases through genome-wide association studies (GWAS) has revealed many disease-associated polymorphisms outside annotated exons or promoter regions. This implies that much disease-relevant regulation may occur from distal regions that rely on three-dimensional contacts to target their associated genes. In this work, we describe two applications of chromosome conformation capture technology that expand our understanding of differentiation and disease. In the first section, we seek to understand and disrupt regulation of a single gene involved in therapeutic resistance in melanoma. In the second and third sections, we identify novel regulators of epidermal differentiation, then create a map of histone modification and contact dynamics during this process to understand how regulators interact with and alter the chromatin environment to facilitate terminal differentiation.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2016 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Barajas, Brook Celia |
|---|---|
| Associated with | Stanford University, Cancer Biology Program. |
| Primary advisor | Khavari, Paul A |
| Thesis advisor | Khavari, Paul A |
| Thesis advisor | Chang, Howard Y. (Howard Yuan-Hao), 1972- |
| Thesis advisor | Greenleaf, William James |
| Thesis advisor | Wysocka, Joanna, Ph. D |
| Advisor | Chang, Howard Y. (Howard Yuan-Hao), 1972- |
| Advisor | Greenleaf, William James |
| Advisor | Wysocka, Joanna, Ph. D |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Brook Celia Barajas. |
|---|---|
| Note | Submitted to the Program in Cancer Biology. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2016. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2016 by Brook Celia Barajas
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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