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Comparative Hi-C Reveals that CTCF Underlies Evolution of Chromosomal Domain Architecture

Rudan, MV; Barrington, C; Henderson, S; Ernst, C; Odom, DT; Tanay, A; Hadjur, S; (2015) Comparative Hi-C Reveals that CTCF Underlies Evolution of Chromosomal Domain Architecture. Cell Reports , 10 (8) pp. 1297-1309. 10.1016/j.celrep.2015.02.004. Green open access

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Abstract

Topological domains are key architectural building blocks of chromosomes, but their functional importance and evolutionary dynamics are not well defined. We performed comparative high-throughput chromosome conformation capture (Hi-C) in four mammals and characterized the conservation and divergence of chromosomal contact insulation and the resulting domain architectures within distantly related genomes. We show that the modular organization of chromosomes is robustly conserved in syntenic regions and that this is compatible with conservation of the binding landscape of the insulator protein CTCF. Specifically, conserved CTCF sites are co-localized with cohesin, are enriched at strong topological domain borders, and bind to DNA motifs with orientations that define the directionality of CTCF’s long-range interactions. Conversely, divergent CTCF binding between species is correlated with divergence of internal domain structure, likely driven by local CTCF binding sequence changes, demonstrating how genome evolution can be linked to a continuous flux of local conformation changes. We also show that large-scale domains are reorganized during genome evolution as intact modules.

Type: Article
Title: Comparative Hi-C Reveals that CTCF Underlies Evolution of Chromosomal Domain Architecture
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.celrep.2015.02.004
Publisher version: http://dx.doi.org/10.1016/j.celrep.2015.02.004
Language: English
Additional information: This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
Keywords: Science & Technology, Life Sciences & Biomedicine, Cell Biology, TRANSCRIPTION FACTOR-BINDING, CHROMATIN INTERACTIONS, DROSOPHILA GENOME, GENE-EXPRESSION, PROTEIN CTCF, COHESIN, ORGANIZATION, SITES, INSULATORS, SEQUENCES
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio
URI: https://discovery.ucl.ac.uk/id/eprint/1465311
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