서브메뉴
검색
Illuminating the 3D Interactions Between Super-Enhancers with Microscopy
Illuminating the 3D Interactions Between Super-Enhancers with Microscopy
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20250211153056
- ISBN
- 9798346385974
- DDC
- 574
- 저자명
- Le, Derek J.
- 서명/저자
- Illuminating the 3D Interactions Between Super-Enhancers with Microscopy
- 발행사항
- [Sl] : Stanford University, 2024
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- 형태사항
- 74 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 86-05, Section: B.
- 주기사항
- Advisor: Boettiger, Alistair.
- 학위논문주기
- Thesis (Ph.D.)--Stanford University, 2024.
- 초록/해제
- 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.
- 일반주제명
- Hybridization
- 일반주제명
- Chromosomes
- 일반주제명
- RNA polymerase
- 일반주제명
- Gene expression
- 일반주제명
- Genomes
- 일반주제명
- Stem cells
- 일반주제명
- Bar codes
- 일반주제명
- Microscopy
- 일반주제명
- Transcription factors
- 일반주제명
- Biochemistry
- 일반주제명
- Bioinformatics
- 일반주제명
- Cellular biology
- 일반주제명
- Genetics
- 기타저자
- Stanford University.
- 기본자료저록
- Dissertations Abstracts International. 86-05B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
008250123s2024 us c eng d■001000017164862
■00520250211153056
■006m o d
■007cr#unu||||||||
■020 ▼a9798346385974
■035 ▼a(MiAaPQ)AAI31643405
■035 ▼a(MiAaPQ)Stanfordxp541sv2618
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a574
■1001 ▼aLe, Derek J.
■24510▼aIlluminating the 3D Interactions Between Super-Enhancers with Microscopy
■260 ▼a[Sl]▼bStanford University▼c2024
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2024
■300 ▼a74 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 86-05, Section: B.
■500 ▼aAdvisor: Boettiger, Alistair.
■5021 ▼aThesis (Ph.D.)--Stanford University, 2024.
■520 ▼aEnhancers 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.
■590 ▼aSchool code: 0212.
■650 4▼aHybridization
■650 4▼aChromosomes
■650 4▼aRNA polymerase
■650 4▼aGene expression
■650 4▼aGenomes
■650 4▼aStem cells
■650 4▼aBar codes
■650 4▼aMicroscopy
■650 4▼aTranscription factors
■650 4▼aBiochemistry
■650 4▼aBioinformatics
■650 4▼aCellular biology
■650 4▼aGenetics
■690 ▼a0487
■690 ▼a0715
■690 ▼a0379
■690 ▼a0369
■71020▼aStanford University.
■7730 ▼tDissertations Abstracts International▼g86-05B.
■790 ▼a0212
■791 ▼aPh.D.
■792 ▼a2024
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17164862▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.


