ArticleCell2015
Disruptions of topological chromatin domains cause pathogenic rewiring of gene-enhancer interactions.
Article in Cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1,249 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1,249 citing papers in PubMed, 1 synthesis or guideline pooled it, 2,236 citations in OpenAlex.
- Cross-platform Hi-C meta-analysis identifies functional insulators that actively block enhancer-promoter interactions.Nature communications · 2026Pooled it
- Identification of Genome-Wide Chromatin Structural Aberration in Cancer by Hi-C Analysis.Methods in molecular biology (Clifton, N.J.) · 2027Article
- Chromosome-level phylogenomics and genome evolution of the grape family.Nature plants · 2026Article
- Tandem duplication upstream ofiScience · 2026Article
- Genomic structural variations distinguishing archaic and modern humans are associated with neurodevelopment.iScience · 2026Article
- Host chromatin architecture in HPV-driven cervical cancer: molecular mechanisms and therapeutic resistance.Medical oncology (Northwood, London, England) · 2026Review
- Structural Variation Sequencing of 26 Amniotic Fluid Samples With Partial Gene Duplications and Postnatal Follow-Up of the Fetuses.Prenatal diagnosis · 2026Article
- Multi-Layer Transcriptomic Comparison Across Human, Pig, and Mouse Informs Tissue- and Trait-Specific Animal Model Selection.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Emergent 3D genome reorganization and graded gene control from the stepwise assembly of transcriptional condensates.Cell reports · 2026Article
- Clustered structural variant hotspots enable oncogenic addiction and plasticity in osteosarcoma.bioRxiv : the preprint server for biology · 2026Article
- Foundation model reveals the shared organization of transcription and topologically associating domains.Cell systems · 2026Article
- Strategies and mechanisms of precision genome engineering: From gene editing to genome writing.iMetaOmics · 2026Review
- Systematic evaluation of the heterogeneity of topologically associating domain boundaries in a large genomic context in humans.NAR genomics and bioinformatics · 2026Article
- Long-read based detection of large copy number variants with potential functional significance using the ContextSV structural variant caller.NAR genomics and bioinformatics · 2026Article
- hicream: A flexible framework to identify significantly different regions in Hi-C data.Bioinformatics (Oxford, England) · 2026Article
- Hi-Cformer enables multiscale chromatin contact map modeling for single-cell Hi-C data analysis.Science advances · 2026Article
- Chromatin accessibility classification of TAD boundaries discloses new architectural proteins.Nucleic acids research · 2026Article
- Gene clustering drives the transcriptional coherence of disparate biological processes in eukaryotes.iScience · 2026Article
- Chromosomal inversions modulate 3D chromatin interactions and regulatory architecture inResearch square · 2026Article
- Allele-specific chromatin architecture shapes imprinted domains and coordinates a distal enhancer and antisense transcription at the mouse Mest-Copg2 domain.Nature communications · 2026Article
1,189 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
Authors and funding
22 authors at 9 institutions in 5 countries.
Funding
Abstract
Mammalian genomes are organized into megabase-scale topologically associated domains (TADs). We demonstrate that disruption of TADs can rewire long-range regulatory architecture and result in pathogenic phenotypes. We show that distinct human limb malformations are caused by deletions, inversions, or duplications altering the structure of the TAD-spanning WNT6/IHH/EPHA4/PAX3 locus. Using CRISPR/Cas genome editing, we generated mice with corresponding rearrangements. Both in mouse limb tissue and patient-derived fibroblasts, disease-relevant structural changes cause ectopic interactions between promoters and non-coding DNA, and a cluster of limb enhancers normally associated with Epha4 is misplaced relative to TAD boundaries and drives ectopic limb expression of another gene in the locus. This rewiring occurred only if the variant disrupted a CTCF-associated boundary domain. Our results demonstrate the functional importance of TADs for orchestrating gene expression via genome architecture and indicate criteria for predicting the pathogenicity of human structural variants, particularly in non-coding regions of the human genome.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.