Cited by 119Genomics and Chromatin DynamicsChromatin Remodeling and CancerChromosomal and Genetic Variations

Dynamics of the 4D Genome during in Vivo Lineage Specification and Differentiation

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Oudelaar, A. Marieke, Beagrie, Robert A., Gosden, Matthew, de Ornellas, Sara, Georgiades, Emily, Kerry, Jon, Hidalgo, Daniel, Carrelha, Joana +8 more·2020·Nature Communications

Published version of a preprint

Abstract

Mammalian gene expression patterns are controlled by regulatory elements, which interact within topologically associating domains (TADs). The relationship between activation of regulatory elements, formation of structural chromatin interactions and gene expression during development is unclear. Here, we present Tiled-C, a low-input chromosome conformation capture (3C) technique. We use this approach to study chromatin architecture at high spatial and temporal resolution through in vivo mouse erythroid differentiation. Integrated analysis of chromatin accessibility and single-cell expression data shows that regulatory elements gradually become accessible within pre-existing TADs during early differentiation. This is followed by structural re-organization within the TAD and formation of specific contacts between enhancers and promoters. Our high-resolution data show that these enhancer-promoter interactions are not established prior to gene expression, but formed gradually during differentiation, concomitant with progressive upregulation of gene activity. Together, these results provide new insight into the close, interdependent relationship between chromatin architecture and gene regulation during development.

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  • Tiled-C was conducted as previously described.

    “Tiled-C, a high-resolution Chromosome Conformation Capture (3C) method that produces contact matrices of selected regions of interest was conducted as previously described.41”
  • In mammalian differentiation models, extensive remodelling of enhancer-promoter contacts is typically observed consistently with enhancer activation.

    “In mammalian differentiation models, in contrast, extensive remodelling of enhancer–promoter contacts is typically observed consistently with enhancer activation [141, 394–397].”

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Authors
Oudelaar, A. M., Beagrie, R. A., Gosden, M., de Ornellas, S., Georgiades, E., Kerry, J., Hidalgo, D., Carrelha, J., Shivalingam, A., El-Sagheer, A. H., Telenius, J. M., Brown, T., Buckle, V. J., Socolovsky, M., Higgs, D. R., & Hughes, J. R.
Affiliations
  • University of Oxford (GB)
  • University of Massachusetts Chan Medical School (US)
  • Suez University (EG)
Corresponding author
  • Higgs, Douglas R.
  • Hughes, Jim R.
Venue
Nature Communications
Published
2020-06-01
Volume
11
Issue
1
Pages
2722-2722
ISSN
2041-1723 (ISSN-L)
OpenAlex
W3030892594
Cited by
119
References
61
Citations by year
2026: 9 · 2025: 20 · 2024: 19 · 2023: 20 · 2022: 17 · 2021: 20 · 2020: 14
FWCI
5.76
Type
journal article
Language
en
Open access
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
Funders
  • RCUK | Medical Research Council
  • Wellcome Trust
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
Keywords
topologically associating domains, chromatin structure, enhancer-promoter interactions, erythroid differentiation, lineage specification, chromatin accessibility, chromosome conformation capture, regulatory elements, single-cell gene expression, mouse embryo
MeSH terms
Mouse Embryonic Stem Cells, Animals, Cell Differentiation, Cells, Cultured, Chromatin, Enhancer Elements, Genetic, Female, Hematopoietic Stem Cells, Mice, Inbred C57BL, Promoter Regions, Genetic, Stem Cells, Genome, Gene Expression Regulation, Developmental, Gene Expression Profiling, Chromosomes, Mammalian, Mice

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