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Illuminating the 3D Interactions Between Super-Enhancers with Microscopy
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  
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MARC

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■020    ▼a9798346385974
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■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.

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