Single-allele chromatin interactions identify regulatory hubs in dynamic compartmentalized domains

The promoters of mammalian genes are commonly regulated by multiple distal enhancers, which physically interact within discrete chromatin domains. How such domains form and how the regulatory elements within them interact in single cells is not understood. To address this we developed Tri-C, a new c...

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Main Authors: Oudelaar, A, Davies, J, Hanssen, L, Telenius, J, Schwessinger, R, Liu, Y, Brown, J, Downes, D, Chiariello, A, Bianco, S, Nicodemi, M, Buckle, V, Dekker, J, Higgs, D, Hughes, J
Format: Journal article
Language:English
Published: Nature Publishing Group 2018
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author Oudelaar, A
Davies, J
Hanssen, L
Telenius, J
Schwessinger, R
Liu, Y
Brown, J
Downes, D
Chiariello, A
Bianco, S
Nicodemi, M
Buckle, V
Dekker, J
Higgs, D
Hughes, J
author_facet Oudelaar, A
Davies, J
Hanssen, L
Telenius, J
Schwessinger, R
Liu, Y
Brown, J
Downes, D
Chiariello, A
Bianco, S
Nicodemi, M
Buckle, V
Dekker, J
Higgs, D
Hughes, J
author_sort Oudelaar, A
collection OXFORD
description The promoters of mammalian genes are commonly regulated by multiple distal enhancers, which physically interact within discrete chromatin domains. How such domains form and how the regulatory elements within them interact in single cells is not understood. To address this we developed Tri-C, a new chromosome conformation capture (3C) approach, to characterize concurrent chromatin interactions at individual alleles. Analysis by Tri-C identifies heterogeneous patterns of single-allele interactions between CTCF boundary elements, indicating that the formation of chromatin domains likely results from a dynamic process. Within these domains, we observe specific higher-order structures that involve simultaneous interactions between multiple enhancers and promoters. Such regulatory hubs provide a structural basis for understanding how multiple cis-regulatory elements act together to establish robust regulation of gene expression.
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spelling oxford-uuid:51921701-5266-44b6-beea-d6139dfaf3d02022-03-26T16:20:23ZSingle-allele chromatin interactions identify regulatory hubs in dynamic compartmentalized domainsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:51921701-5266-44b6-beea-d6139dfaf3d0EnglishSymplectic Elements at OxfordNature Publishing Group2018Oudelaar, ADavies, JHanssen, LTelenius, JSchwessinger, RLiu, YBrown, JDownes, DChiariello, ABianco, SNicodemi, MBuckle, VDekker, JHiggs, DHughes, JThe promoters of mammalian genes are commonly regulated by multiple distal enhancers, which physically interact within discrete chromatin domains. How such domains form and how the regulatory elements within them interact in single cells is not understood. To address this we developed Tri-C, a new chromosome conformation capture (3C) approach, to characterize concurrent chromatin interactions at individual alleles. Analysis by Tri-C identifies heterogeneous patterns of single-allele interactions between CTCF boundary elements, indicating that the formation of chromatin domains likely results from a dynamic process. Within these domains, we observe specific higher-order structures that involve simultaneous interactions between multiple enhancers and promoters. Such regulatory hubs provide a structural basis for understanding how multiple cis-regulatory elements act together to establish robust regulation of gene expression.
spellingShingle Oudelaar, A
Davies, J
Hanssen, L
Telenius, J
Schwessinger, R
Liu, Y
Brown, J
Downes, D
Chiariello, A
Bianco, S
Nicodemi, M
Buckle, V
Dekker, J
Higgs, D
Hughes, J
Single-allele chromatin interactions identify regulatory hubs in dynamic compartmentalized domains
title Single-allele chromatin interactions identify regulatory hubs in dynamic compartmentalized domains
title_full Single-allele chromatin interactions identify regulatory hubs in dynamic compartmentalized domains
title_fullStr Single-allele chromatin interactions identify regulatory hubs in dynamic compartmentalized domains
title_full_unstemmed Single-allele chromatin interactions identify regulatory hubs in dynamic compartmentalized domains
title_short Single-allele chromatin interactions identify regulatory hubs in dynamic compartmentalized domains
title_sort single allele chromatin interactions identify regulatory hubs in dynamic compartmentalized domains
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