Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 19 of 19 for “"3D chromatin"”.
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Sculpting 3d Chromatin Folding Via Genome Editing
… and initiated contacts reflective of chromatin loop extrusion. Deletions of the CBS or the TSS individually or in combination within inserts revealed their distinct contributions to genome folding. Altogether, short DNA insertions can suffice to shape the spatial genome in a manner …
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Changes of nucleosome positioning and 3D chromatin organization in cell transitions
… the nucleus in a highly condensed form called chromatin. The basic unit of chromatin is the nucleosome. The positioning of nucleosomes on the DNA determines the accessibility of transcription factors (TFs) and other regulatory molecules. Beyond nucleosome positioning, the higher level of 3D …
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Single-molecule G-quadruplex visualisation in live cells and 3D chromatin
… the potential involvement of G4s in 3D chromatin organisation. For this, G4 imaging was extended into 3D by super-resolution microscopy in fixed cells, and combined with single-cell Hi-C method. Hi-C is a fixed nucleus chromatin conformation capture technique that can simulate 3D …
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3D Chromatin Structure and Gene Regulation: Integrated Genome Structure, Transcriptomics and Epigenetics
The three-dimensional (3D) organization of the genome is essential for regulating gene expression, replication, and stability. Chromatin folding mediates enhancer–promoter communication, but bulk Hi-C data obscure single-cell variability, while sparse single-cell Hi-C limits structural resolution. …
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Investigating the function of DNA G-quadruplex structures in human enhancers
… (G4s) are four-stranded DNA three-dimensional (3D) structures, that form in guanine-rich regions of the genome. G4s are enriched at sites of important regulatory potential in diverse genomes, including promoters and enhancers. Enhancers interact with target promoters through 3D folding of …
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Role of Polycomb Group Protein Mel18 in Hematopoietic Stem Cell Maintenance
… lysine 119 (H2AK119ub1). PRC1 can also regulate 3D chromatin structure. Bmi1 (PCGF4) and Mel18 (PCGF2) are two major homologs of the PCGF subunit within the canonical PRC1 complex. While Bmi1 is a positive regulator of hematopoietic stem cells (HSCs) and leukemia stem cells (LSCs) self-renewal, …
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Computational Analysis of Transcriptional Regulation
… Key features of this are the three-dimensional (3D) chromatin organisation of eukaryotic genomes and the post-transcriptional control of RNA fates. Eukaryotic nuclear DNA is tightly packaged as chromatin that is further folded into higher order structures. The 3D folding of eukaryotic genome …
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THE IMPACT OF REPLICATION STRESS ON THE EPIGENOME OF MOUSE EMBRYONIC STEM CELLS
Epigenetic reprogramming and chromatin structure guide differentiation and define cell identity during embryogenesis. To maintain cell identity and genome integrity, epigenetic marks are faithfully inherited during DNA replication through tightly coordinated processes. Our recent work demonstrated …
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The role of MLL4 in the chromatin framework: from the epigenome to 3D genome organization
… it is perpetuated at the topological level of chromatin, remains not fully understood. This issue is particularly relevant given that mutations in the gene coding for MLL4 (KMT2D) are responsible for a rare multi-systemic disorder named Kabuki syndrome, which currently has inadequate …
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On the physics of intranuclear organization
… and functional packaging of DNA into chromatin is mediated by phase separation. Epigenetic modifications of histone proteins, which DNA wraps around to form nucleosomes, are key determinants of nucleosomes’ condensability and chromatin’s higher-order structure. Chromatin structure, by …
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The pathological and genomic impact of CTCF depletion in mammalian model systems
… regulatory domains. In doing so, it insulates chromatin and fine-tunes gene activation, repression, and silencing. Complete removal of CTCF from mammalian cells causes catastrophic genomic dysregulation, most likely due to widespread collapse of 3D chromatin looping within the nucleus. In …
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IDENTIFICATION OF CANCER- AND METASTASIS-RELATED EPIGENETIC DYNAMICS USING PATIENT-DERIVED ORGANOIDS
… their histone mark profiling through chromatin immunoprecipitation followed by sequencing (ChIP-seq). In order to provide a global genome-wide annotation of chromatin regions, we evaluated the combinatorial distribution of five histone marks (H3K27ac, H3K4me1, H3K4me3, H3K36me3 and …
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Leveraging Genomic Information for Safer Gene Therapy
… insertions (pMEIs) along with epigenetic and 3D chromatin information to identify new genomic safe harbor (GSH) sites. Out of 19 blood specific and 5 brain specific GSH sites, we experimentally validated 3 GSH sites from blood which showed stable transgene expression without disruption of …
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Characterizing the Role of TLX1 in T-cell Acute Lymphoblastic Leukemia
… changes in gene expression, epigenetics, chromatin accessibility, and 3D chromatin conformation at multiple stages of oncogenic transformation. TLX1 T-ALL human samples translocated TLX1 to the TCRδ locus and had diverse secondary mutations, and TLX1 strongly colocalized with the BAF …
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Transcriptional and structural control of cell identity genes
… expression within a larger three-dimensional (3D) chromatin architecture, but these structures and their functions are poorly understood. Chapter 3 presents a study in which Cohesin ChIA-PET data was generated to identify the local chromosomal structures at both active and repressed genes …
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Data-driven Mechanistic Modeling of 3D Human Genome
Three-dimensional (3D) organization of the human genome regulates DNA-templated processes, including gene transcription, gene regulation, and DNA replication, which are crucial for cell differentiation and cell functionality. Computational modeling serves as an efficient and effective way of …
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The Nucleosome Remodelling & Deacetylase complex: Genome folding & transcriptional regulation
… on the three dimensional organisation of chromatin within a cell’s nucleus. Approximately 2 metres of DNA is folded to fit within a nucleus which is on the order of a few micrometers. In addition to simply fitting within the space available, this folding directly influences gene …
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Computational approaches for analyzing regulatory regions in the human genome
… somatic mutations, and 3) in the context of 3D chromatin organization. In the first part of this dissertation, we explored the functions of the lineage-specific TFBS in the human genome using ANTICE, a novel probabilistic algorithm developed by us. Compared to previous methods, ANTICE is …
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Gene misexpression in humans
… I did not observe misexpression occurring via 3D chromatin architecture rearrangements as reported in certain rare diseases. Chapter 4 was completed while conducting a three month placement at AstraZeneca. In this chapter, I developed a machine learning model to classify short open reading …