ArticleGenome biology2020
Tandem CTCF sites function as insulators to balance spatial chromatin contacts and topological enhancer-promoter selection.
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 51 papers, 1 of them a synthesis that pooled it.
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Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 84 citations in OpenAlex.
- Cross-platform Hi-C meta-analysis identifies functional insulators that actively block enhancer-promoter interactions.Nature communications · 2026Pooled it
- CTCF delimits a DNA methylation transition at the intergenic region between the embryonic and adult α-globin genes.Epigenetics · 2026Article
- ETV6 Rearrangement Suppresses CDKN1B Transcription by Disrupting an Intragenic Super-enhancer in Acute Lymphoblastic Leukemia.Cancer research · 2026Article
- A cardiac-related, promoter-proximal, regulatory element shapes chromatin and JAG1 transcription.Life science alliance · 2026Article
- WAVE2 and REST/NRSF Regulate Clustered Gene Expression by Maintaining Heterochromatin Organization.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Wiz regulates clustered protocadherin genes by restricting CTCF/cohesin loop extrusion in a genomic-distance biased manner.PLoS genetics · 2026Article
- Tandem repeats in human brain evolution and disease susceptibility.Molecules and cells · 2026Review
- RFX5 as a regulator of spatial chromatin contacts and gene expression.Communications biology · 2026Article
- Understanding super enhancers in genome architecture and their roles in livestock breeding.BMC genomics · 2026Review
- The Biological Function of Genome Organization.International journal of molecular sciences · 2025Review
- Ectopic Recruitment of the CTCF N-Terminal Domain with Two Proximal Zinc-Finger Domains as a Tool for 3D Genome Engineering.International journal of molecular sciences · 2025Article
- Multifaceted regulation of the HOX cluster and its implications in oral cancer.Clinical epigenetics · 2025Article
- CTCF Point Mutation at R567 Disrupts Mouse Heart Development via 3D Genome Rearrangement and Transcription Dysregulation.Cell proliferation · 2025Article
- Gaining insights into Alzheimer's disease by predicting chromatin spatial organization.Bioinformatics advances · 2025Article
- A negatively charged region within carboxy-terminal domain maintains proper CTCF DNA binding.iScience · 2024Article
- Review
- CTCF mutation at R567 causes developmental disorders via 3D genome rearrangement and abnormal neurodevelopment.Nature communications · 2024Article
- DNA methylation patterns of transcription factor binding regions characterize their functional and evolutionary contexts.Genome biology · 2024Article
- TEAD2 initiates ground-state pluripotency by mediating chromatin looping.The EMBO journal · 2024Article
- Genetic variation is a key determinant of chromatin accessibility and drives differences in the regulatory landscape of C57BL/6J and 129S1/SvImJ mice.Nucleic acids research · 2024Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCTCF is a key insulator-binding protein, and mammalian genomes contain numerous CTCF sites, many of which are organized in tandem.
resultsUsing CRISPR DNA-fragment editing, in conjunction with chromosome conformation capture, we find that CTCF sites, if located between enhancers and promoters in the protocadherin (Pcdh) and β-globin clusters, function as an enhancer-blocking insulator by forming distinct directional chromatin loops, regardless whether enhancers contain CTCF sites or not. Moreover, computational simulation in silico and genetic deletions in vivo as well as dCas9 blocking in vitro revealed balanced promoter usage in cell populations and stochastic monoallelic expression in single cells by large arrays of tandem CTCF sites in the Pcdh and immunoglobulin heavy chain (Igh) clusters. Furthermore, CTCF insulators promote, counter-intuitively, long-range chromatin interactions with distal directional CTCF sites, consistent with the cohesin "loop extrusion" model. Finally, gene expression levels are negatively correlated with CTCF insulators located between enhancers and promoters on a genome-wide scale. Thus, single CTCF insulators ensure proper enhancer insulation and promoter activation while tandem CTCF topological insulators determine balanced spatial contacts and promoter choice.
conclusionsThese findings have interesting implications on the role of topological chromatin insulators in 3D genome folding and developmental gene regulation.
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