The three-dimensional genome: principles and roles of long-distance interactions
- PMID: 26852111
- PMCID: PMC4887315
- DOI: 10.1016/j.ceb.2016.01.009
The three-dimensional genome: principles and roles of long-distance interactions
Abstract
The linear sequence of eukaryotic genomes is arranged in a specific manner within the three-dimensional nuclear space. Interactions between distant sites partition the genome into domains of highly associating chromatin. Interaction domains are found in many organisms, but their properties and the principles governing their establishment vary between different species. Topologically associating domains (TADs) extending over large genomic regions are found in mammals and Drosophila melanogaster, whereas other types of contact domains exist in lower eukaryotes. Here we review recent studies that explore the mechanisms by which long distance chromatin interactions determine the 3D organization of the genome and the relationship between this organization and the establishment of specific patterns of gene expression.
Copyright © 2016 Elsevier Ltd. All rights reserved.
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- Lupiáñez DG, Kraft K, Heinrich V, Krawitz P, Brancati F, Klopocki E, Horn D, Kayserili H, Opitz JM, Laxova R, et al. Disruptions of topological chromatin domains cause pathogenic rewiring of gene-enhancer interactions. Cell. 2015;161:1012–1025. This study examined chromatin interactions in patients with limb malformations and found that each was associated with disruption of a TAD boundary. Deletion of TAD borders resulted in increased interactions from genes to neighboring TADs containing enhancer elements. This suggested that enhancers act past the previous TAD border which results in misregulation of gene expression. - PMC - PubMed
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- Li L, Lyu X, Hou C, Takenaka N, Nguyen HQ, Ong C-T, Cubeñas-Potts C, Hu M, Lei EP, Bosco G, et al. Widespread rearrangement of 3D chromatin organization underlies polycomb-mediated stress-induced silencing. Mol Cell. 2015;58:216–231. Through comparison of Hi-C contact maps in normal and heat-shocked Drosophila cells it was shown that TAD organization and architectural protein localization can change drastically in response to environmental stimuli. This study also explored effects of transcription inhibition on long-range chromatin interactions, as well as the knockdown of key aarchitectural proteins. - PMC - PubMed
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