ArticleNature genetics2018
Dynamic 3D chromatin architecture contributes to enhancer specificity and limb morphogenesis.
Article in Nature genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers.
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Who cites it
113 citing papers in PubMed, 210 citations in OpenAlex.
- Epigenetic regulation of vertebrate limb development: from field specification to tissue morphogenesis.Epigenetics · 2026Review
- Mechanisms and functional implications of long-range enhancer-dependent gene regulation.Nature genetics · 2026Review
- De novo structural variants in autism spectrum disorder disrupt distal regulatory interactions of neuronal genes.Genome research · 2026Article
- ATRX inactivation disrupts global chromatin state and topology to dysregulate neurodevelopmental pathways in glioma pathogenesis.Nucleic acids research · 2026Article
- OptoLoop - an optogenetic tool to probe the functional role of genome organization.Journal of cell science · 2026Article
- Cohesin-mediated loop extrusion and enhancer-associated factors additively contribute toGenes & development · 2026Article
- Whole-genome 3D architectural screen reveals modulators of brain DNA structure.bioRxiv : the preprint server for biology · 2026Article
- The role of cohesin loading at enhancers in the flux of loop extrusion and long-range transcriptional control.bioRxiv : the preprint server for biology · 2026Article
- Polymorphic 3D genome architecture mediated by transposable elements.bioRxiv : the preprint server for biology · 2026Article
- Temporal constraints on enhancer usage shape the regulation of limb gene transcription.Nature communications · 2026Article
- 3D Chromatin Architecture During Early Development: New Methods and New Findings.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Mandibular Prognathism in Dolang Sheep: Hi-C Evidence for Localized TAD Remodeling at Craniofacial Loci.Animals : an open access journal from MDPI · 2025Article
- Functional architecture of cardiac TF regulatory landscapes in control of mammalian heart development.bioRxiv : the preprint server for biology · 2025Article
- Reporter CRISPR screens decipher cis-regulatory and trans-regulatory principles at the Xist locus.Nature structural & molecular biology · 2025Article
- OptoLoop: An optogenetic tool to probe the functional role of genome organization.bioRxiv : the preprint server for biology · 2025Article
- Redundant and Singular Regulatory Elements Underlie the Rapidly Evolving Pigmentation of Drosophila.Molecular biology and evolution · 2025Article
- Direction and modality of transcription changes caused by TAD boundary disruption in Slc29a3/Unc5b locus depends on tissue-specific epigenetic context.Epigenetics & chromatin · 2025Article
- Chromatin landscape alteration uncovers multiple transcriptional circuits during memory CD8+ T-cell differentiation.Protein & cell · 2025Article
- Chromatin interaction-based annotation of regulatory elements reveals dynamic promoter-enhancer interactions in lymphocyte development.iScience · 2025Article
- Liebenberg syndrome severity arises from variations in Pitx1 locus topology and proportion of ectopically transcribing cells.Nature communications · 2025Article
53 more citing papers are in PubMed but not listed here.
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Authors and funding
24 authors at 6 institutions in 3 countries.
Funding
Abstract
The regulatory specificity of enhancers and their interaction with gene promoters is thought to be controlled by their sequence and the binding of transcription factors. By studying Pitx1, a regulator of hindlimb development, we show that dynamic changes in chromatin conformation can restrict the activity of enhancers. Inconsistent with its hindlimb-restricted expression, Pitx1 is controlled by an enhancer (Pen) that shows activity in forelimbs and hindlimbs. By Capture Hi-C and three-dimensional modeling of the locus, we demonstrate that forelimbs and hindlimbs have fundamentally different chromatin configurations, whereby Pen and Pitx1 interact in hindlimbs and are physically separated in forelimbs. Structural variants can convert the inactive into the active conformation, thereby inducing Pitx1 misexpression in forelimbs, causing partial arm-to-leg transformation in mice and humans. Thus, tissue-specific three-dimensional chromatin conformation can contribute to enhancer activity and specificity in vivo and its disturbance can result in gene misexpression and disease.
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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.