ArticleNature communications2023
Outward-oriented sites within clustered CTCF boundaries are key for intra-TAD chromatin interactions and gene regulation.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 14 citations in OpenAlex.
- 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
- Chromatin accessibility classification of TAD boundaries discloses new architectural proteins.Nucleic acids research · 2026Article
- Wiz regulates clustered protocadherin genes by restricting CTCF/cohesin loop extrusion in a genomic-distance biased manner.PLoS genetics · 2026Article
- RFX5 as a regulator of spatial chromatin contacts and gene expression.Communications biology · 2026Article
- Integrating Hi-C data and RNA-seq data to reveal the 3D genome in sheep.BMC genomics · 2025Article
- CRISPR live-cell imaging reveals chromatin dynamics and enhancer interactions at multiple non-repetitive loci.Nature biotechnology · 2025Article
- Structural variants in the 3D genome as drivers of disease.Nature reviews. Genetics · 2025Review
- 3D Genome Architecture in Stem Cell Lineage Commitment: from Structural Organization to Precision Regulation.Advanced genetics (Hoboken, N.J.) · 2025Review
- Nucleosome organization of mouse embryos during pre-implantation development.Scientific reports · 2025Article
- 3D Genome Engineering: Current Advances and Therapeutic Opportunities in Human Diseases.Research (Washington, D.C.) · 2025Review
- A negatively charged region within carboxy-terminal domain maintains proper CTCF DNA binding.iScience · 2024Article
- Cooperative insulation of regulatory domains by CTCF-dependent physical insulation and promoter competition.Nature communications · 2024Article
- Chromatin insulator mechanisms ensure accurate gene expression by controlling overall 3D genome organization.Current opinion in genetics & development · 2024Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
CTCF plays an important role in 3D genome organization by adjusting the strength of chromatin insulation at TAD boundaries, where clustered CBS (CTCF-binding site) elements are often arranged in a tandem array with a complex divergent or convergent orientation. Here, using Pcdh and HOXD loci as a paradigm, we look into the clustered CTCF TAD boundaries and find that, counterintuitively, outward-oriented CBS elements are crucial for inward enhancer-promoter interactions as well as for gene regulation. Specifically, by combinatorial deletions of a series of putative enhancer elements in mice in vivo or CBS elements in cultured cells in vitro, in conjunction with chromosome conformation capture and RNA-seq analyses, we show that deletions of outward-oriented CBS elements weaken the strength of long-distance intra-TAD promoter-enhancer interactions and enhancer activation of target genes. Our data highlight the crucial role of outward-oriented CBS elements within the clustered CTCF TAD boundaries in developmental gene regulation and have interesting implications on the organization principles of clustered CTCF sites within TAD boundaries.
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Registered trials
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