Enhancer hubs and loop collisions identified from single-allele topologies.

Autor: Allahyar A; Center for Molecular Medicine, University Medical Center, Utrecht University, Utrecht, the Netherlands.; Delft Bioinformatics Lab, Faculty of Electrical Engineering, Mathematics and Computer Science, Delft University of Technology, Delft, the Netherlands., Vermeulen C; Oncode Institute, Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, the Netherlands., Bouwman BAM; Oncode Institute, Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, the Netherlands., Krijger PHL; Oncode Institute, Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, the Netherlands., Verstegen MJAM; Oncode Institute, Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, the Netherlands., Geeven G; Oncode Institute, Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, the Netherlands., van Kranenburg M; Oncode Institute, Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, the Netherlands., Pieterse M; Oncode Institute, Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, the Netherlands., Straver R; Center for Molecular Medicine, University Medical Center, Utrecht University, Utrecht, the Netherlands., Haarhuis JHI; Division of Gene Regulation, Netherlands Cancer Institute, Amsterdam, the Netherlands., Jalink K; Division of Cell Biology, Netherlands Cancer Institute, Amsterdam, the Netherlands., Teunissen H; Oncode Institute and Division of Gene Regulation, Netherlands Cancer Institute, Amsterdam, the Netherlands., Renkens IJ; Center for Molecular Medicine, University Medical Center, Utrecht University, Utrecht, the Netherlands., Kloosterman WP; Center for Molecular Medicine, University Medical Center, Utrecht University, Utrecht, the Netherlands., Rowland BD; Division of Gene Regulation, Netherlands Cancer Institute, Amsterdam, the Netherlands., de Wit E; Oncode Institute and Division of Gene Regulation, Netherlands Cancer Institute, Amsterdam, the Netherlands., de Ridder J; Center for Molecular Medicine, University Medical Center, Utrecht University, Utrecht, the Netherlands. j.deridder-4@umcutrecht.nl., de Laat W; Oncode Institute, Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, the Netherlands. w.delaat@hubrecht.eu.
Jazyk: angličtina
Zdroj: Nature genetics [Nat Genet] 2018 Aug; Vol. 50 (8), pp. 1151-1160. Date of Electronic Publication: 2018 Jul 09.
DOI: 10.1038/s41588-018-0161-5
Abstrakt: Chromatin folding contributes to the regulation of genomic processes such as gene activity. Existing conformation capture methods characterize genome topology through analysis of pairwise chromatin contacts in populations of cells but cannot discern whether individual interactions occur simultaneously or competitively. Here we present multi-contact 4C (MC-4C), which applies Nanopore sequencing to study multi-way DNA conformations of individual alleles. MC-4C distinguishes cooperative from random and competing interactions and identifies previously missed structures in subpopulations of cells. We show that individual elements of the β-globin superenhancer can aggregate into an enhancer hub that can simultaneously accommodate two genes. Neighboring chromatin domain loops can form rosette-like structures through collision of their CTCF-bound anchors, as seen most prominently in cells lacking the cohesin-unloading factor WAPL. Here, massive collision of CTCF-anchored chromatin loops is believed to reflect 'cohesin traffic jams'. Single-allele topology studies thus help us understand the mechanisms underlying genome folding and functioning.
Databáze: MEDLINE
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