Enhancer-promoter interactions are reconfigured through the formation of long-range multiway chromatin hubs as mouse ES cells exit pluripotency Article Swipe
David Lando
,
Xiaoyan Ma
,
Yaqiang Cao
,
Aleksandra Jartseva
,
Tim J. Stevens
,
Wayne Boucher
,
Nicola Reynolds
,
Bertille Montibus
,
Dominic Hall
,
Andreas Lackner
,
Ramy Ragheb
,
Martin Leeb
,
Brian Hendrich
,
Ernest D. Laue
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1101/2023.02.08.527615
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1101/2023.02.08.527615
Summary Enhancers are genomic DNA sequences that bind transcription factors, chromatin regulators and non-coding transcripts to modulate the expression of target genes. They have been found to act from different locations relative to a gene and to modulate the activity of promoters up to ∼1 Mb away. Here we report the first 3D genome structures of single mouse ES cells as they are induced to exit pluripotency, transition through a formative stage and undergo neuroectodermal differentiation. In order to directly study how interactions between enhancers and promoters are reconfigured genome wide we have determined 3D structures of haploid cells using single cell Hi-C, where we can unambiguously map the contacts to particular chromosomes. We find that there is a remarkable reorganisation of 3D genome structure where inter-chromosomal intermingling increases dramatically in the formative state. This intermingling is associated with the formation of a large number of multiway hubs that bring together enhancers and promoters with similar chromatin states from typically 5-8 distant chromosomal sites that are often separated by many Mb from each other. Genes important for pluripotency exit establish contacts with emerging enhancers within multiway chromatin hubs as cells enter the formative state, consistent with these structural changes playing an important role in establishing new cell identities. Furthermore, we find that different multiway chromatin hubs, and thus different enhancer-promoter interactions, are formed in different individual cells. Our results suggest that studying genome structure in single cells will be important to identify key changes in enhancer-promoter interactions that occur as cells undergo developmental transitions.
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Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2023.02.08.527615
- https://www.biorxiv.org/content/biorxiv/early/2023/02/08/2023.02.08.527615.full.pdf
- OA Status
- green
- Cited By
- 2
- References
- 74
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4319459892
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4319459892Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1101/2023.02.08.527615Digital Object Identifier
- Title
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Enhancer-promoter interactions are reconfigured through the formation of long-range multiway chromatin hubs as mouse ES cells exit pluripotencyWork title
- Type
-
preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
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2023Year of publication
- Publication date
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2023-02-08Full publication date if available
- Authors
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David Lando, Xiaoyan Ma, Yaqiang Cao, Aleksandra Jartseva, Tim J. Stevens, Wayne Boucher, Nicola Reynolds, Bertille Montibus, Dominic Hall, Andreas Lackner, Ramy Ragheb, Martin Leeb, Brian Hendrich, Ernest D. LaueList of authors in order
- Landing page
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https://doi.org/10.1101/2023.02.08.527615Publisher landing page
- PDF URL
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https://www.biorxiv.org/content/biorxiv/early/2023/02/08/2023.02.08.527615.full.pdfDirect link to full text PDF
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-
YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
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https://www.biorxiv.org/content/biorxiv/early/2023/02/08/2023.02.08.527615.full.pdfDirect OA link when available
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Enhancer, Chromatin, Biology, Promoter, Genome, Gene, Computational biology, Genetics, Transcription (linguistics), Transcription factor, Gene expression, Philosophy, LinguisticsTop concepts (fields/topics) attached by OpenAlex
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2Total citation count in OpenAlex
- Citations by year (recent)
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2024: 1, 2023: 1Per-year citation counts (last 5 years)
- References (count)
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74Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.haploid | 97 |
| abstract_inverted_index.induced | 63 |
| abstract_inverted_index.playing | 199 |
| abstract_inverted_index.results | 228 |
| abstract_inverted_index.similar | 155 |
| abstract_inverted_index.suggest | 229 |
| abstract_inverted_index.through | 68 |
| abstract_inverted_index.undergo | 73, 251 |
| abstract_inverted_index.activity | 39 |
| abstract_inverted_index.contacts | 109, 180 |
| abstract_inverted_index.directly | 79 |
| abstract_inverted_index.emerging | 182 |
| abstract_inverted_index.factors, | 9 |
| abstract_inverted_index.identify | 241 |
| abstract_inverted_index.modulate | 16, 37 |
| abstract_inverted_index.multiway | 146, 185, 213 |
| abstract_inverted_index.relative | 31 |
| abstract_inverted_index.studying | 231 |
| abstract_inverted_index.together | 150 |
| abstract_inverted_index.Enhancers | 1 |
| abstract_inverted_index.chromatin | 10, 156, 186, 214 |
| abstract_inverted_index.different | 29, 212, 218, 224 |
| abstract_inverted_index.enhancers | 84, 151, 183 |
| abstract_inverted_index.establish | 179 |
| abstract_inverted_index.formation | 140 |
| abstract_inverted_index.formative | 70, 132, 192 |
| abstract_inverted_index.important | 175, 201, 239 |
| abstract_inverted_index.increases | 128 |
| abstract_inverted_index.locations | 30 |
| abstract_inverted_index.promoters | 41, 86, 153 |
| abstract_inverted_index.separated | 167 |
| abstract_inverted_index.sequences | 5 |
| abstract_inverted_index.structure | 124, 233 |
| abstract_inverted_index.typically | 159 |
| abstract_inverted_index.associated | 137 |
| abstract_inverted_index.consistent | 194 |
| abstract_inverted_index.determined | 93 |
| abstract_inverted_index.expression | 18 |
| abstract_inverted_index.individual | 225 |
| abstract_inverted_index.non-coding | 13 |
| abstract_inverted_index.particular | 111 |
| abstract_inverted_index.regulators | 11 |
| abstract_inverted_index.remarkable | 119 |
| abstract_inverted_index.structural | 197 |
| abstract_inverted_index.structures | 54, 95 |
| abstract_inverted_index.transition | 67 |
| abstract_inverted_index.chromosomal | 162 |
| abstract_inverted_index.identities. | 207 |
| abstract_inverted_index.transcripts | 14 |
| abstract_inverted_index.Furthermore, | 208 |
| abstract_inverted_index.chromosomes. | 112 |
| abstract_inverted_index.dramatically | 129 |
| abstract_inverted_index.establishing | 204 |
| abstract_inverted_index.interactions | 82, 246 |
| abstract_inverted_index.pluripotency | 177 |
| abstract_inverted_index.reconfigured | 88 |
| abstract_inverted_index.transitions. | 253 |
| abstract_inverted_index.developmental | 252 |
| abstract_inverted_index.interactions, | 220 |
| abstract_inverted_index.intermingling | 127, 135 |
| abstract_inverted_index.pluripotency, | 66 |
| abstract_inverted_index.transcription | 8 |
| abstract_inverted_index.unambiguously | 106 |
| abstract_inverted_index.reorganisation | 120 |
| abstract_inverted_index.neuroectodermal | 74 |
| abstract_inverted_index.differentiation. | 75 |
| abstract_inverted_index.enhancer-promoter | 219, 245 |
| abstract_inverted_index.inter-chromosomal | 126 |
| cited_by_percentile_year.max | 94 |
| cited_by_percentile_year.min | 89 |
| corresponding_author_ids | https://openalex.org/A5076130320, https://openalex.org/A5081370013 |
| countries_distinct_count | 2 |
| institutions_distinct_count | 14 |
| corresponding_institution_ids | https://openalex.org/I21196054, https://openalex.org/I241749 |
| citation_normalized_percentile.value | 0.63393894 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |