ArticleCell reports2017
The Conserved Sonic Hedgehog Limb Enhancer Consists of Discrete Functional Elements that Regulate Precise Spatial Expression.
Article in Cell reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 72 citations in OpenAlex.
- Epigenetic regulation of vertebrate limb development: from field specification to tissue morphogenesis.Epigenetics · 2026Review
- Mechanisms underlying disease-causing variants in promoters and enhancers.Nature genetics · 2026Review
- Characterization of a cis-regulatory element upstream of matrix metalloproteinase-9.Scientific reports · 2025Article
- Exploring the roles of conserved context-dependent cis-regulatory elements (cdCREs) in multicellularity, human health and disease.The FEBS journal · 2025Review
- Systematic enhancer mapping and functional analysis in zebrafish with optimized CRISPR interference.Nucleic acids research · 2025Article
- Bystander activation across a TAD boundary supports a cohesin-dependent transcription cluster model for enhancer function.Genes & development · 2025Article
- The exit from naive pluripotency: a platform for the study of enhancer mechanistics.Biochemical Society transactions · 2025Review
- Enhancer regulation in cancer: from epigenetics to mArchives of pharmacal research · 2025Review
- Caudal fin shape imprinted during late zebrafish embryogenesis is re-patterned by the Sonic hedgehog pathway.PLoS biology · 2025Article
- Epigenetic priming of mammalian embryonic enhancer elements coordinates developmental gene networks.Genome biology · 2025Article
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- The 3' region of the ZPA regulatory sequence (ZRS) is required for activity and contains a critical E-box.Frontiers in cell and developmental biology · 2025Article
- Evidence for Fgf and Wnt regulation ofFrontiers in cell and developmental biology · 2025Article
- Anterior-posterior constraint on Hedgehog signaling by hhip in teleost fin elaboration.Development (Cambridge, England) · 2024Article
- Development of a ZRS Reporter System for the Newt (Biomedicines · 2024Article
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- Rapid and Quantitative Functional Interrogation of Human Enhancer Variant Activity in Live Mice.bioRxiv : the preprint server for biology · 2023Article
- What is an enhancer?BioEssays : news and reviews in molecular, cellular and developmental biology · 2023Review
- Developmental regulation of conserved non-coding element evolution provides insights into limb loss in squamates.Science China. Life sciences · 2023Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Expression of sonic hedgehog (Shh) in the limb bud is regulated by an enhancer called the zone of polarizing activity regulatory sequence (ZRS), which, in evolution, belongs to an ancient group of highly conserved cis regulators found in all classes of vertebrates. Here, we examined the endogenous ZRS in mice, using genome editing to establish the relationship between enhancer composition and embryonic phenotype. We show that enhancer activity is a consolidation of distinct activity domains. Spatial restriction of Shh expression is mediated by a discrete repressor module, whereas levels of gene expression are controlled by large overlapping domains containing varying numbers of HOXD binding sites. The number of HOXD binding sites regulates expression levels incrementally. Substantial portions of conserved sequence are dispensable, indicating the presence of sequence redundancy. We propose a collective model for enhancer activity in which function is an integration of discrete expression activities and redundant components that drive robust expression.
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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.