"""TSA-Seq"": a novel proximity mapping approach for studying three dimensional genome organization and function"
type: CreativeWork
description: "The organization of chromatin and its localization in the eukaryotic cell nucleus plays a critical role in gene regulation (Agarwal and Rao, 1998; Brown, 2003; Ferrai et al., 2010) and is important for maintaining normal genome function. However, although it is known that the distribution of chromatin and genes in the eukaryotic cell nucleus is non-random and dynamic, the actual domain organization of chromatin, the mechanisms and dynamics which give rise to this domain organization, and the functional relationship between chromosome domain organization and transcriptional regulation are all unknown. The major technical limitations hindering research related to these problems include the difficulties in direct visualization of large scale chromatin structure, the lack of an efficient mapping approach to identify DNA position and distribution in the three dimensional (3D) nuclear space, and the inability to connect three dimensional microscopic information with the linear genome sequence. In this dissertation, I describe ""TSA-Seq"", a novel proximity mapping approach I have developed to study 3D genome organization. TSA-Seq transfers cytological distance information into a genomic plot, allowing us to detect chromosome spatial organization relative to any nuclear compartment. Using this method, I studied 3D genome organization by mapping the average distances of the entire genome relative to two major nuclear compartments- nuclear speckles and the nuclear lamina. We discovered that proximity to the nuclear lamina or to nuclear speckles correspond to the two extremes of the transcriptionally inactive versus active spectrum, with levels of gene expression and timing of replication distributed along this lamina-speckle-axis such that chromosome regions with the highest transcriptional activity associate closest to nuclear speckles and furthest away from the nuclear lamina. We demonstrated the ability of detecting chromatin loops and mean chromatin compaction rates fro…
abstract: "The organization of chromatin and its localization in the eukaryotic cell nucleus plays a critical role in gene regulation (Agarwal and Rao, 1998; Brown, 2003; Ferrai et al., 2010) and is important for maintaining normal genome function. However, although it is known that the distribution of chromatin and genes in the eukaryotic cell nucleus is non-random and dynamic, the actual domain organization of chromatin, the mechanisms and dynamics which give rise to this domain organization, and the functional relationship between chromosome domain organization and transcriptional regulation are all unknown. The major technical limitations hindering research related to these problems include the difficulties in direct visualization of large scale chromatin structure, the lack of an efficient mapping approach to identify DNA position and distribution in the three dimensional (3D) nuclear space, and the inability to connect three dimensional microscopic information with the linear genome sequence. In this dissertation, I describe ""TSA-Seq"", a novel proximity mapping approach I have developed to study 3D genome organization. TSA-Seq transfers cytological distance information into a genomic plot, allowing us to detect chromosome spatial organization relative to any nuclear compartment. Using this method, I studied 3D genome organization by mapping the average distances of the entire genome relative to two major nuclear compartments- nuclear speckles and the nuclear lamina. We discovered that proximity to the nuclear lamina or to nuclear speckles correspond to the two extremes of the transcriptionally inactive versus active spectrum, with levels of gene expression and timing of replication distributed along this lamina-speckle-axis such that chromosome regions with the highest transcriptional activity associate closest to nuclear speckles and furthest away from the nuclear lamina. We demonstrated the ability of detecting chromatin loops and mean chromatin compaction rates fro…
author: Chen, Yu
language: en
keywords: TSA-Seq, 3D genome organization, nuclear speckles, nuclear Lamina
date published: 2016-11-10T18:27:45Z
date modified: 2026-07-22T22:26:35Z
provider: University of Illinois - Urbana-Champaign
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Illinois at Urbana-Champaign

PropertyValue
property ID: Handle
value: http://hdl.handle.net/2142/92935