ArticleGenome biology2020
Spatial patterns of CTCF sites define the anatomy of TADs and their boundaries.
Article in Genome biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed.
- Chromatin accessibility classification of TAD boundaries discloses new architectural proteins.Nucleic acids research · 2026Article
- Evolution of CTCF binding sites in the human genome.Molecular biology and evolution · 2026Article
- SMARCD1 and Its Functional Relevance in SWI/SNF and Cancer.International journal of molecular sciences · 2026Review
- TADShop: systematic benchmarking and identification of topologically associating domains.Nature methods · 2026Article
- A wavelet-based approach generates quantitative, scale-free and hierarchical descriptions of 3D genome structures and new biological insights.PLoS computational biology · 2026Article
- A split luciferase biosensing platform for detection and imaging of chromatin loops in individual live cells.Nucleic acids research · 2025Article
- Generating three-dimensional genome structures with a variational quantum algorithm.Briefings in bioinformatics · 2025Article
- Role of Histone H3 Lysine 4 Methylation in Chromatin Biology.Molecules (Basel, Switzerland) · 2025Review
- CRISPR-based functional genomics tools in vertebrate models.Experimental & molecular medicine · 2025Review
- EBNA leader protein orchestrates chromatin architecture remodeling during Epstein-Barr virus-induced B cell transformation.Nucleic acids research · 2025Article
- A multi-tissue and -breed catalogue of chromatin conformations and their implications in gene regulation in pigs.BMC genomics · 2025Article
- Identifying deleterious noncoding variation through gain and loss of CTCF binding activity.American journal of human genetics · 2025Article
- Integrating Single-Molecule Sequencing and Deep Learning to Predict Haplotype-Specific 3D Chromatin Organization in a Mendelian Condition.bioRxiv : the preprint server for biology · 2025Article
- CTCF-mediated insulation and chromatin environment modulate Car5b escape from X inactivation.BMC biology · 2025Article
- A guide to studying 3D genome structure and dynamics in the kidney.Nature reviews. Nephrology · 2025Review
- Motif distribution in genomes gives insights into gene clustering and co-regulation.Nucleic acids research · 2025Article
- Gaining insights into Alzheimer's disease by predicting chromatin spatial organization.Bioinformatics advances · 2025Article
- Beyond the Synapse:International journal of molecular sciences · 2024Review
- Single-cell RNA sequencing algorithms underestimate changes in transcriptional noise compared to single-molecule RNA imaging.Cell reports methods · 2024Article
- Active enhancers: recent research advances and insights into disease.Biology direct · 2024Review
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3 authors.
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Abstract
backgroundTopologically associating domains (TADs) are genomic regions of self-interaction. Additionally, it is known that TAD boundaries are enriched in CTCF binding sites. In turn, CTCF sites are known to be asymmetric, whereby the convergent configuration of a pair of CTCF sites leads to the formation of a chromatin loop in vivo. However, to date, it has been unclear how to reconcile TAD structure with CTCF-based chromatin loops.
resultsWe approach this problem by analysing CTCF binding site strengths and classifying clusters of CTCF sites along the genome on the basis of their relative orientation. Analysis of CTCF site orientation classes as a function of their spatial distribution along the human genome reveals that convergent CTCF site clusters are depleted while divergent CTCF clusters are enriched in the 5- to 100-kb range. We then analyse the distribution of CTCF binding sites as a function of TAD boundary conservation across seven primary human blood cell types. This reveals divergent CTCF site enrichment at TAD boundaries. Furthermore, convergent arrays of CTCF sites separate the left and right sections of TADs that harbour internal CTCF sites, resulting in unequal TAD 'halves'.
conclusionsThe orientation-based CTCF binding site cluster classification that we present reconciles TAD boundaries and CTCF site clusters in a mechanistically elegant fashion. This model suggests that the emergent structure of nuclear chromatin in the form of TADs relies on the obligate alternation of divergent and convergent CTCF site clusters that occur at different length scales along the genome.
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