The interplay of global chromosomal organisation, promoter-enhancer interactions and transcription
type: CreativeWork
description: All somatic cells within an organism contain the same genetic material, yet they display pronounced differences in function and morphology. Precise control of gene expression is of fundamental importance to allow cells to properly develop, maintain homeostasis, and respond to external stimuli. The first step in gene expression is transcription, which starts at the core promoter region. While core promoters are crucial for transcriptional initiation, they are insufficient for establishing complex tissue- and condition-specific gene expression patterns in multicellular organisms. Additional transcriptional control elements, such as gene enhancers, are required for this, with many such elements localising considerable distances away from their target promoters. Enhancers commonly convey their regulatory signals to target promoters by forming physical contacts with them through three-dimensional DNA looping, underpinning the importance of chromosomal organisation in transcriptional control. In recent years, the emergence of chromosome conformation capture and related methodologies has dramatically increased our understanding of chromosomal organisation. In particular, high-throughput Hi-C analyses across cell types have led to the identification of spatial genomic structures, including Topologically Associating Domains (TADs). In parallel, high-resolution versions of these technologies (such as 5C, CHiA-PET, HiChIP and Capture Hi-C) have detected multitudes of novel looping interactions, including connections between promoters and enhancers. The interplay between precise regulatory interactions, the higher-order chromosomal organisation, and their joint contribution to transcriptional control is incompletely understood and is the focus of this work. In the first part of this work, I take advantage of high-resolution Promoter Capture Hi-C (PCHi-C) data to investigate the localisation of promoter interactions with respect to TAD boundaries in human primary blood cells and…
abstract: All somatic cells within an organism contain the same genetic material, yet they display pronounced differences in function and morphology. Precise control of gene expression is of fundamental importance to allow cells to properly develop, maintain homeostasis, and respond to external stimuli. The first step in gene expression is transcription, which starts at the core promoter region. While core promoters are crucial for transcriptional initiation, they are insufficient for establishing complex tissue- and condition-specific gene expression patterns in multicellular organisms. Additional transcriptional control elements, such as gene enhancers, are required for this, with many such elements localising considerable distances away from their target promoters. Enhancers commonly convey their regulatory signals to target promoters by forming physical contacts with them through three-dimensional DNA looping, underpinning the importance of chromosomal organisation in transcriptional control. In recent years, the emergence of chromosome conformation capture and related methodologies has dramatically increased our understanding of chromosomal organisation. In particular, high-throughput Hi-C analyses across cell types have led to the identification of spatial genomic structures, including Topologically Associating Domains (TADs). In parallel, high-resolution versions of these technologies (such as 5C, CHiA-PET, HiChIP and Capture Hi-C) have detected multitudes of novel looping interactions, including connections between promoters and enhancers. The interplay between precise regulatory interactions, the higher-order chromosomal organisation, and their joint contribution to transcriptional control is incompletely understood and is the focus of this work. In the first part of this work, I take advantage of high-resolution Promoter Capture Hi-C (PCHi-C) data to investigate the localisation of promoter interactions with respect to TAD boundaries in human primary blood cells and…
author: Thiecke, Michiel
language: eng
keywords: Promoter interactions, CTCF, SCC1, Cohesin, Topologically Associating Domains, TADs, PCHiC, Promoter Capture Hi-C, ATAC-seq, ChIP-seq, RNA-seq, SLAM-seq, RT-PCR, qPCR, Genome organisation, Spatial genome, Epigenetics, Transcriptional regulation, Transcriptomics, Transcription, Cell cycle synchronisation, Targeted protein degradation, Rapid protein degradation, Auxin degron, Sequencing, Bioinformatics, Data analysis, Statistical analysis, Regression, LASSO regression, Logistic regression, Ordinal logistic regression, Genome wide, HeLa, Haematopoietic cells, BRD4
license: https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/7987aa38-590d-43fb-ba8a-4834f6941e87/download
license: https://www.rioxx.net/licenses/all-rights-reserved/
date published: 2020-04-24
date modified: 2026-07-22T22:24:08Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.56339