Please use this identifier to cite or link to this item:
http://hdl.handle.net/1942/29081
Title: | Spatial chromatin architecture alteration by structural variations in human genomes at the population scale | Authors: | Sadowski, Michal Kraft, Agnieszka SZALAJ, Przemek Wlasnowolski, Michal Tang, Zhonghui Ruan, Yijun Plewczynski, Dariusz |
Issue Date: | 2019 | Publisher: | BMC | Source: | GENOME BIOLOGY, 20 (Art N° 148) | Abstract: | BackgroundThe number of reported examples of chromatin architecture alterations involved in the regulation of gene transcription and in disease is increasing. However, no genome-wide testing has been performed to assess the abundance of these events and their importance relative to other factors affecting genome regulation. This is particularly interesting given that a vast majority of genetic variations identified in association studies are located outside coding sequences. This study attempts to address this lack by analyzing the impact on chromatin spatial organization of genetic variants identified in individuals from 26 human populations and in genome-wide association studies.ResultsWe assess the tendency of structural variants to accumulate in spatially interacting genomic segments and design an algorithm to model chromatin conformational changes caused by structural variations. We show that differential gene transcription is closely linked to the variation in chromatin interaction networks mediated by RNA polymerase II. We also demonstrate that CTCF-mediated interactions are well conserved across populations, but enriched with disease-associated SNPs. Moreover, we find boundaries of topological domains as relatively frequent targets of duplications, which suggest that these duplications can be an important evolutionary mechanism of genome spatial organization.ConclusionsThis study assesses the critical impact of genetic variants on the higher-order organization of chromatin folding and provides insight into the mechanisms regulating gene transcription at the population scale, of which local arrangement of chromatin loops seems to be the most significant. It provides the first insight into the variability of the human 3D genome at the population scale. | Notes: | [Sadowski, Michal; Kraft, Agnieszka; Szalaj, Przemyslaw; Wlasnowolski, Michal; Plewczynski, Dariusz] Univ Warsaw, Ctr New Technol, Banacha 2c, PL-02097 Warsaw, Poland. [Sadowski, Michal] Univ Warsaw, Fac Phys, Pasteura 5, PL-02093 Warsaw, Poland. [Kraft, Agnieszka; Wlasnowolski, Michal; Plewczynski, Dariusz] Warsaw Univ Technol, Fac Math & Informat Sci, Koszykowa 75, PL-00662 Warsaw, Poland. [Szalaj, Przemyslaw] Med Univ Bialystok, Ctr Innovat Res, Kilinskiego 1, PL-15089 Bialystok, Poland. [Szalaj, Przemyslaw] Hasselt Univ, I BioStat, Agoralaan Bldg D, BE-3590 Diepenbeek, Belgium. [Tang, Zhonghui] Sun Yat Sen Univ, Zhongshan Sch Med, Guangzhou 510080, Guangdong, Peoples R China. [Ruan, Yijun] Jackson Lab Genom Med, 10 Discovery Dr, Farmington, CT 06032 USA. | Keywords: | Genomics; Chromatin architecture; Topologically associating domains; Chromatin loops; Genome regulation; Gene transcription; CCCTC-binding factor; RNA polymerase II; Biophysical modeling; Human;Genomics; Chromatin architecture; Topologically associating domains; Chromatin loops; Genome regulation; Gene transcription; CCCTC-binding factor; RNA polymerase II; Biophysical modeling; Human | Document URI: | http://hdl.handle.net/1942/29081 | ISSN: | 1474-760X | e-ISSN: | 1474-760X | DOI: | 10.1186/s13059-019-1728-x | ISI #: | 000477962600001 | Rights: | The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2020 |
Appears in Collections: | Research publications |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
sadowski 1.pdf | Published version | 8.2 MB | Adobe PDF | View/Open |
SCOPUSTM
Citations
6
checked on Sep 2, 2020
WEB OF SCIENCETM
Citations
25
checked on Oct 19, 2024
Page view(s)
104
checked on Sep 7, 2022
Download(s)
168
checked on Sep 7, 2022
Google ScholarTM
Check
Altmetric
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.