ArticleDevelopment (Cambridge, England)2016
Shh and ZRS enhancer colocalisation is specific to the zone of polarising activity.
Article in Development (Cambridge, England), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
What it found
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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.
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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.
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Who cites it
83 citing papers in PubMed, 129 citations in OpenAlex.
- Epigenetic regulation of vertebrate limb development: from field specification to tissue morphogenesis.Epigenetics · 2026Review
- Connecting multiway enhancer-promoter interactions to changes in gene expression in cancer.bioRxiv : the preprint server for biology · 2026Article
- Early determination of the dorsal-ventral axis in endochondral ossification in mice.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2025Article
- Nanoscale dynamics of enhancer-promoter interactions during exit from pluripotency.Nucleic acids research · 2025Article
- The exit from naive pluripotency: a platform for the study of enhancer mechanistics.Biochemical Society transactions · 2025Review
- A transcription coupling model for how enhancers communicate with their target genes.Nature structural & molecular biology · 2025Review
- Epigenetics in Learning and Memory.Sub-cellular biochemistry · 2025Review
- Multiple allelic configurations govern long-range Shh enhancer-promoter communication in the embryonic forebrain.Molecular cell · 2024Article
- Genetic analysis of preaxial polydactyly: identification of novel variants and the role of ZRS duplications in a Chinese cohort of 102 cases.Human genetics · 2024Article
- Cell type- and transcription-independent spatial proximity between enhancers and promoters.Molecular biology of the cell · 2024Article
- Transcription decouples estrogen-dependent changes in enhancer-promoter contact frequencies and spatial proximity.PLoS genetics · 2024Article
- Enhancer-promoter specificity in gene transcription: molecular mechanisms and disease associations.Experimental & molecular medicine · 2024Review
- Article
- Topology regulatory elements: From shaping genome architecture to gene regulation.Current opinion in structural biology · 2023Review
- Dispersal of PRC1 condensates disrupts polycomb chromatin domains and loops.Life science alliance · 2023Article
- Hnrnpk is essential for embryonic limb bud development as a transcription activator and a collaborator of insulator protein Ctcf.Cell death and differentiation · 2023Article
- Three-dimensional genome structure and function.MedComm · 2023Review
- Review
- Enhancer Function in the 3D Genome.Genes · 2023Review
- 3D enhancer-promoter interactions and multi-connected hubs: Organizational principles and functional roles.Cell reports · 2023Review
23 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Limb-specific Shh expression is regulated by the (∼1 Mb distant) ZRS enhancer. In the mouse, limb bud-restricted spatiotemporal Shh expression occurs from ∼E10 to E11.5 at the distal posterior margin and is essential for correct autopod formation. Here, we have analysed the higher-order chromatin conformation of Shh in expressing and non-expressing tissues, both by fluorescence in situ hybridisation (FISH) and by chromosome conformation capture (5C). Conventional and super-resolution light microscopy identified significantly elevated frequencies of Shh/ZRS colocalisation only in the Shh-expressing regions of the limb bud, in a conformation consistent with enhancer-promoter loop formation. However, in all tissues and at all developmental stages analysed, Shh-ZRS spatial distances were still consistently shorter than those to a neural enhancer located between Shh and ZRS in the genome. 5C identified a topologically associating domain (TAD) over the Shh/ZRS genomic region and enriched interactions between Shh and ZRS throughout E11.5 embryos. Shh/ZRS colocalisation, therefore, correlates with the spatiotemporal domain of limb bud-specific Shh expression, but close Shh and ZRS proximity in the nucleus occurs regardless of whether the gene or enhancer is active. We suggest that this constrained chromatin configuration optimises the opportunity for the active enhancer to locate and instigate the expression of Shh.
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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.