Enhancer hubs and loop collisions identified from single-allele topologies

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Enhancer hubs and loop collisions identified from single-allele topologies

Journal Article (2018)

Author(s)

Amin Allahyar (University Medical Center Utrecht, TU Delft - Pattern Recognition and Bioinformatics)

Carlo Vermeulen (NCG-KNAW, University Medical Center Utrecht)

Britta A.M. Bouwman (NCG-KNAW, University Medical Center Utrecht)

Peter H.L. Krijger (University Medical Center Utrecht, NCG-KNAW)

Marjon J.A.M. Verstegen (NCG-KNAW, University Medical Center Utrecht)

Geert Geeven (University Medical Center Utrecht, NCG-KNAW)

Mark Pieterse (University Medical Center Utrecht, NCG-KNAW)

Roy Straver (University Medical Center Utrecht)

Kees Jalink (Swammerdam Institute for Life Sciences, Nederlands Kanker Instituut - Antoni van Leeuwenhoek ziekenhuis, Van Leeuwenhoek Centre for Advanced Microscopy)

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Research Group

Pattern Recognition and Bioinformatics

DOI related publication

https://doi.org/10.1038/s41588-018-0161-5

To reference this document use:

https://resolver.tudelft.nl/uuid:f2719fbb-d94a-4ca7-9751-0697ffb85167

More Info

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Publication Year

2018

Language

English

Research Group

Pattern Recognition and Bioinformatics

Journal title

Nature Genetics

Volume number

50

Pages (from-to)

1151-1160

Downloads counter

297

Abstract

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.

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