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Review
. 2016 Jun:40:8-14.
doi: 10.1016/j.ceb.2016.01.009. Epub 2016 Feb 4.

The three-dimensional genome: principles and roles of long-distance interactions

Affiliations
Review

The three-dimensional genome: principles and roles of long-distance interactions

M Jordan Rowley et al. Curr Opin Cell Biol. 2016 Jun.

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.

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Figures

Figure 1
Figure 1. Chromosome Organization in Eukaryotes
Chromatin interactions detected by Hi-C displayed as heatmaps for human [47] (A); D. melanogaster [4] (B); C. elegans [12] (C); A. thaliana [9] (D); S. pombe [14] (E); and S. cerevisiae [15] (F). A) Large TADs in mammals occur with CTCF in reverse – forward orientation at domain borders. Arrows indicate CTCF motif orientation connected by chromatin interactions (red arcs). B) Clustering of architectural proteins at domain borders. High occupancy architectural binding sites (APBS) correlate with domain borders in D. melanogaster. C) The Dosage Compensation Complex (DCC) binds domain borders in C. elegans hermaphrodites. Interaction domains are stronger on the X chromosome in C. elegans and correlate with condensin-containing DCC binding sites. D) Architectural proteins in A. thaliana are unknown. A. thaliana has distinct chromatin interaction structures (indicated by arrow). E) Globule domains in S. pombe. Cohesin (displayed as rings) sites correlate with edges of globule domains. F) Small domains in S. cerevisiae. Micro-C allows high resolution contact maps and identification of short chromatin interaction domains. Cohesin (displayed as rings) loader Scc2 correlates with domain borders.
Figure 2
Figure 2. Changes to Domain Organization
A) Hi-C of human embryonic stem cells (H1 ESC – bottom right) compared to lung fibroblast cells (IMR90 – top left) [47]. Arrows indicate TAD structure changes. B) Hi-C of D. melanogaster under heat shock (bottom right) compared to normal temperature (top left) [4].

References

    1. Cubeñas-Potts C, Corces VG. Architectural proteins, transcription, and the three-dimensional organization of the genome. FEBS Lett. 2015;589:2923–2930. - PMC - PubMed
    1. Dekker J, Misteli T. Long-Range Chromatin Interactions. Cold Spring Harb Perspect Biol. 2015:7. - PMC - PubMed
    1. 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
    1. 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
    1. Apostolou E, Ferrari F, Walsh RM, Bar-Nur O, Stadtfeld M, Cheloufi S, Stuart HT, Polo JM, Ohsumi TK, Borowsky ML, et al. Genome-wide chromatin interactions of the Nanog locus in pluripotency, differentiation, and reprogramming. Cell Stem Cell. 2013;12:699–712. - PMC - PubMed

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