Enhancer hubs and loop collisions identified from single-allele topologies

Amin Allahyar; Carlo Vermeulen; Britta A M Bouwman; Peter H L Krijger; Marjon J A M Verstegen; Geert Geeven; Melissa van Kranenburg; Mark Pieterse; Roy Straver; Judith H I Haarhuis; Kees Jalink; Hans Teunissen; Ivo J Renkens; Wigard P Kloosterman; Benjamin D Rowland; Elzo de Wit; Jeroen de Ridder; Wouter de Laat

doi:10.1038/s41588-018-0161-5

Enhancer hubs and loop collisions identified from single-allele topologies

Amin Allahyar, Carlo Vermeulen, Britta A M Bouwman, Peter H L Krijger, Marjon J A M Verstegen, Geert Geeven, Melissa van Kranenburg, Mark Pieterse, Roy Straver, Judith H I Haarhuis, Kees Jalink, Hans Teunissen, Ivo J Renkens, Wigard P Kloosterman, Benjamin D Rowland, Elzo de Wit, Jeroen de Ridder, Wouter de Laat

Hubrecht Institute

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgave › Artikel › Wetenschappelijk › peer review

164 Citaten (Scopus)

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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.

Originele taal-2	Engels
Pagina's (van-tot)	1151-1160
Aantal pagina's	10
Tijdschrift	Nature Genetics
Volume	50
Nummer van het tijdschrift	8
DOI's	https://doi.org/10.1038/s41588-018-0161-5
Status	Gepubliceerd - aug. 2018

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Allahyar, A., Vermeulen, C., Bouwman, B. A. M., Krijger, P. H. L., Verstegen, M. J. A. M., Geeven, G., van Kranenburg, M., Pieterse, M., Straver, R., Haarhuis, J. H. I., Jalink, K., Teunissen, H., Renkens, I. J., Kloosterman, W. P., Rowland, B. D., de Wit, E., de Ridder, J., & de Laat, W. (2018). Enhancer hubs and loop collisions identified from single-allele topologies. Nature Genetics, 50(8), 1151-1160. https://doi.org/10.1038/s41588-018-0161-5

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title = "Enhancer hubs and loop collisions identified from single-allele topologies",

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.",

author = "Amin Allahyar and Carlo Vermeulen and Bouwman, {Britta A M} and Krijger, {Peter H L} and Verstegen, {Marjon J A M} and Geert Geeven and {van Kranenburg}, Melissa and Mark Pieterse and Roy Straver and Haarhuis, {Judith H I} and Kees Jalink and Hans Teunissen and Renkens, {Ivo J} and Kloosterman, {Wigard P} and Rowland, {Benjamin D} and {de Wit}, Elzo and {de Ridder}, Jeroen and {de Laat}, Wouter",

year = "2018",

month = aug,

doi = "10.1038/s41588-018-0161-5",

language = "English",

volume = "50",

pages = "1151--1160",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

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Allahyar, A, Vermeulen, C, Bouwman, BAM, Krijger, PHL, Verstegen, MJAM, Geeven, G, van Kranenburg, M, Pieterse, M, Straver, R, Haarhuis, JHI, Jalink, K, Teunissen, H, Renkens, IJ, Kloosterman, WP, Rowland, BD, de Wit, E, de Ridder, J & de Laat, W 2018, 'Enhancer hubs and loop collisions identified from single-allele topologies', Nature Genetics, vol. 50, nr. 8, blz. 1151-1160. https://doi.org/10.1038/s41588-018-0161-5

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AU - Vermeulen, Carlo

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AU - Verstegen, Marjon J A M

AU - Geeven, Geert

AU - van Kranenburg, Melissa

AU - Pieterse, Mark

AU - Straver, Roy

AU - Haarhuis, Judith H I

AU - Jalink, Kees

AU - Teunissen, Hans

AU - Renkens, Ivo J

AU - Kloosterman, Wigard P

AU - Rowland, Benjamin D

AU - de Wit, Elzo

AU - de Ridder, Jeroen

AU - de Laat, Wouter

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AB - 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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JO - Nature Genetics

JF - Nature Genetics

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ER -

Enhancer hubs and loop collisions identified from single-allele topologies

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