Enhancer accessibility and CTCF occupancy underlie asymmetric TAD architecture and cell type specific genome topology
Open accessAbstract
Cohesin and CTCF are master regulators of genome topology. How these ubiquitous proteins contribute to cell-type specific genome structure is poorly understood. Here, we explore quantitative aspects of topologically associated domains (TAD) between pluripotent embryonic stem cells (ESC) and lineage-committed cells. ESCs exhibit permissive topological configurations which manifest themselves as increased inter- TAD interactions, weaker intra-TAD interactions, and a unique intra-TAD connectivity whereby one border makes pervasive interactions throughout the domain. Such ‘stripe’ domains are associated with both poised and active chromatin landscapes and transcription is not a key determinant of their structure. By tracking the developmental dynamics of stripe domains, we show that stripe formation is linked to the functional state of the cell through cohesin loading at lineage-specific enhancers and developmental control of CTCF binding site occupancy. We propose that the unique topological configuration of stripe domains represents a permissive landscape facilitating both productive and opportunistic gene regulation and is important for cellular identity.
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Stripe domains tend to anchor at a single CTCF binding site, which points towards a nearby site for the cohesin-loading factor NIPBL.
“Stripe domains tend to anchor at a single CTCF binding site (as opposed to two divergent CTCF sites in the classic case for TADs), which points towards a nearby site for the cohesin-loading factor NIPBL [456, 457].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [457]
The Results sections on CTCF occupancy and enhancer accessibility (page unavailable) report a prominent CTCF site and maximal NIPBL signal at the anchored border of stripe domains. They do not say that the CTCF site points toward a nearby NIPBL site; they also report multiple CTCF-binding sites within stripe domains, so the 'single site' description is too strong. (LLM, conf=0.86)
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- Authors
- Barrington, C., Georgopoulou, D., Pezic, D., Varsally, W., Herrero, J., & Hadjur, S.
- Affiliations
- The Francis Crick Institute (GB)
- University of Cambridge (GB)
- University College London (GB)
- Corresponding author
- Hadjur, Suzana
- Venue
- Nature Communications
- Published
- 2019-07-02
- Volume
- 10
- Issue
- 1
- Pages
- 2908-2908
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC6606583
- OpenAlex
- W2954613863
- Cited by
- 102
- References
- 25
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 14 · 2023: 27 · 2022: 12 · 2021: 13 · 2020: 16 · 2019: 3
- FWCI
- 3.64
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- Apollo (cc-by)
- Funders
- Wellcome Trust (106985/Z/15/Z)
- 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, enhancer accessibility, CTCF binding, cohesin, genome topology, stripe domains, embryonic stem cells, lineage commitment, chromatin looping, developmental dynamics, cell identity, chromatin accessibility
- MeSH terms
- Protein Domains, CCCTC-Binding Factor, Cohesins, Chromatin, Chromosomal Proteins, Non-Histone, Enhancer Elements, Genetic, Protein Binding, Species Specificity, Cell Cycle Proteins, Cell Lineage, Pluripotent Stem Cells
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