자료유형  

 학위논문

Control Number  

0017164862

International Standard Book Number  

9798346385974

Dewey Decimal Classification Number  

574

Main Entry-Personal Name  

Le, Derek J.

Publication, Distribution, etc. (Imprint  

[S.l.] : Stanford University., 2024

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2024

Physical Description  

74 p.

General Note  

Source: Dissertations Abstracts International, Volume: 86-05, Section: B.

General Note  

Advisor: Boettiger, Alistair.

Dissertation Note  

Thesis (Ph.D.)--Stanford University, 2024.

Summary, Etc.  

요약Enhancers are non-protein coding sequences in the genome that help promote transcription of genes. Enhancer sequences are typically bound by transcription factors that regulate lineage- and cell type-specific genes for proper cell function and development. Traditionally, this regulatory effect is thought to occur through pairwise, physical looping of the enhancer sequence to its target promoter in proximal 3D space, allowing proteins at the enhancer to be in contact with proteins at the promoter. However, recent discoveries have observed 3D configurations and interactions that are less consistent with a pairwise contact-driven model and more consistent with a multivalent "hub" model with multiple enhancers and promoters interacting within a common space in the nucleus.To address this gap of knowledge, my dissertation focuses on characterizing interactions between super-enhancers (SEs) as a model of multiway enhancer and promoter interactions. Super-enhancers were chosen based on their previously described properties: (1) enriched to regulate genes important for cell identity and function that could potentially be coregulated; (2) exceptionally occupied by TFs and coactivators that were shown or hypothesized to cluster; and (3) their detection in multiway SE-SE interactions with proximity-ligation free methods, genome architecture mapping and split-pool recognition of interactions by tag extension. Utilizing optical reconstruction of chromatin architecture, a single-cell, sequential fluorescent in situhybridization method, I found that SE interaction clusters are rare at close contact thresholds. However, a larger contact threshold identified SE communities that assemble cooperatively and are associated with decreasing linear genomic distance, RNA Pol2 and Med1 occupancy, and nuclear compartmentalization. Moreover, SE communities are also associated with increased transcriptional bursting, challenging both pairwise and hub models in the context of SE-mediated transcriptional regulation.

Subject Added Entry-Topical Term  

Hybridization.

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Chromosomes.

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RNA polymerase.

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Gene expression.

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Genomes.

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Stem cells.

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Bar codes.

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Microscopy.

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Transcription factors.

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Biochemistry.

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Bioinformatics.

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Cellular biology.

Subject Added Entry-Topical Term  

Genetics.

Added Entry-Corporate Name  

Stanford University.

Host Item Entry  

Dissertations Abstracts International. 86-05B.

Electronic Location and Access  

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Control Number  

joongbu:654285