ArticleCurrent biology : CB2016
Shadow Enhancers Are Pervasive Features of Developmental Regulatory Networks.
Article in Current biology : CB, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 146 papers.
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Who cites it
146 citing papers in PubMed, 269 citations in OpenAlex.
- Developmental expression of the skeletal muscle determination gene,bioRxiv : the preprint server for biology · 2026Article
- Genome architecture shapes the evolutionary origins of redundant enhancers in fly and mouse.bioRxiv : the preprint server for biology · 2026Article
- Distinct mechanisms decommission redundant enhancers to facilitate phenotypic evolution.Science advances · 2026Article
- Enhancer Trajectories in Lineage Commitment: Regulatory Logic of States and Cooperation.Biomolecules · 2026Review
- Functional architecture of cardiac TF regulatory landscapes in control of mammalian heart development.bioRxiv : the preprint server for biology · 2025Article
- Multiple cis-regulatory modules ensure robust tup/islet1 function in dorsal muscle identity specification.Skeletal muscle · 2025Article
- Biological roles of enhancer RNA m6A modification and its implications in cancer.Cell communication and signaling : CCS · 2025Review
- Enhancer RNA transcription pinpoints functional genetic variants linked to asthma.Nature communications · 2025Article
- An Osteoblast-Specific Enhancer and Subenhancer Cooperatively RegulateInternational journal of molecular sciences · 2025Article
- Comprehensive dissection of cis-regulatory elements in a 2.8 Mb topologically associated domain in six human cancers.Nature communications · 2025Article
- Genetic coupling of enhancer activity and connectivity in gene expression control.Nature communications · 2025Article
- Two coacting shadow enhancers regulate twin of eyeless expression during early Drosophila development.Genetics · 2025Article
- Decoding the epigenetics and chromatin loop dynamics of androgen receptor-mediated transcription.Nature communications · 2024Article
- A Foxf1-Wnt-Nr2f1 cascade promotes atrial cardiomyocyte differentiation in zebrafish.PLoS genetics · 2024Article
- The case against simplistic genetic explanations of evolution.Development (Cambridge, England) · 2024Review
- Article
- A gene desert required for regulatory control of pleiotropic Shox2 expression and embryonic survival.Nature communications · 2024Article
- EnhancerNet: a predictive model of cell identity dynamics through enhancer selection.Development (Cambridge, England) · 2024Article
- Rare variation in non-coding regions with evolutionary signatures contributes to autism spectrum disorder risk.Cell genomics · 2024Article
- Transcriptomic Response to Pyrethroid Treatment in Closely Related Bed Bug Strains Varying in Resistance.Genome biology and evolution · 2024Article
86 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
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Embryogenesis is remarkably robust to segregating mutations and environmental variation; under a range of conditions, embryos of a given species develop into stereotypically patterned organisms. Such robustness is thought to be conferred, in part, through elements within regulatory networks that perform similar, redundant tasks. Redundant enhancers (or "shadow" enhancers), for example, can confer precision and robustness to gene expression, at least at individual, well-studied loci. However, the extent to which enhancer redundancy exists and can thereby have a major impact on developmental robustness remains unknown. Here, we systematically assessed this, identifying over 1,000 predicted shadow enhancers during Drosophila mesoderm development. The activity of 23 elements, associated with five genes, was examined in transgenic embryos, while natural structural variation among individuals was used to assess their ability to buffer against genetic variation. Our results reveal three clear properties of enhancer redundancy within developmental systems. First, it is much more pervasive than previously anticipated, with 64% of loci examined having shadow enhancers. Their spatial redundancy is often partial in nature, while the non-overlapping function may explain why these enhancers are maintained within a population. Second, over 70% of loci do not follow the simple situation of having only two shadow enhancers-often there are three (rols), four (CadN and ade5), or five (Traf1), at least one of which can be deleted with no obvious phenotypic effects. Third, although shadow enhancers can buffer variation, patterns of segregating variation suggest that they play a more complex role in development than generally considered.
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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.