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A Cis-Regulatory Lexicon of Dna Motif Combinations Mediating Cell Type-Specific Gene Regulation.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	A Cis-Regulatory Lexicon of Dna Motif Combinations Mediating Cell Type-Specific Gene Regulation./
作者:	Donohue, Laura Kaitlin Hill.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2021,
面頁冊數:	124 p.
附註:	Source: Dissertations Abstracts International, Volume: 83-05, Section: B.
Contained By:	Dissertations Abstracts International83-05B.
標題:	Cancer. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28827981
ISBN:	9798494461483

A Cis-Regulatory Lexicon of Dna Motif Combinations Mediating Cell Type-Specific Gene Regulation.
Donohue, Laura Kaitlin Hill.

A Cis-Regulatory Lexicon of Dna Motif Combinations Mediating Cell Type-Specific Gene Regulation. - Ann Arbor : ProQuest Dissertations & Theses, 2021 - 124 p.

Source: Dissertations Abstracts International, Volume: 83-05, Section: B.

Thesis (Ph.D.)--Stanford University, 2021.

This item must not be sold to any third party vendors.

The role of the DNA sequence in protein-coding genes has been widely established due to the obvious functional relevance and well-defined relationships between DNA variation and protein sequence. However, most disease-associated variants are not in protein-coding sequences. This has led to much investigation of non-coding variation as it relates to protein-coding gene regulation. Critically, non-coding regulatory elements within DNA are intricately linked to cell type-specific protein-coding gene expression. This dissertation contributes to the goal of uncovering the underlying cis-regulatory logic of non-coding DNA sequences driving cell type-specific gene expression in homeostasis and disease. Cell type-specific non-coding cis-regulatory elements are known to drive important gene expression programs. However, it is still unclear what combinatorial DNA sequences underlie cell type-specific gene regulatory mechanisms. The objective of this dissertation is to progress our understanding of cis-regulatory logic through integration of genome-wide regulatory maps followed by modeling of combinatorial DNA motif logic in cis-regulatory modules regulating cell type-specific gene expression programs and focused identification of functional regulatory DNA motif combinations (DMCs) in homeostasis and complex disease. In Chapter 2, I generate epigenomic and transcriptomic profiles of 15 primary human cell types and perform integrated analysis to define cell type-specific open chromatin peak-long range looped-expressed target gene transcripts (PLTs). I then incorporate disease-associated single nucleotide variants (SNVs) from the NHGRI GWAS catalog and Genotype-Tissue Expression (GTEx) data to link SNVs enriched in cell type-specific PLTs to putative target genes. In Chapter 3, I model the genomic information necessary to derive cis-regulatory modules linked to cell type-specific gene expression programs and nominate transcription factor (TF) DMCs underlying cell type-specific regulatory logic. Finally, in Chapter 4, I validate DMC logic in four primary human cell types and identify cancer-specific regulatory logic in human squamous cell carcinoma and melanoma cells. The findings and approaches described in this dissertation add to the existing annotation of functional combinatorial TF motif logic and help build a framework for future studies of cis-regulatory logic.

ISBN: 9798494461483Subjects--Topical Terms:

634186
Cancer.

A Cis-Regulatory Lexicon of Dna Motif Combinations Mediating Cell Type-Specific Gene Regulation.
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