ArticleNature communications2025
Uncovering hidden enhancers through unbiased in vivo testing.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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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
9 citing papers in PubMed.
- Temporal loss ofGenes & development · 2026Article
- Convergence of external and internal stressors on a stress-responsive enhancer of theProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Facilitators may represent a new class of regulatory elements.Current opinion in genetics & development · 2026Review
- CRISPR tiling deletion screens reveal functional enhancers and allelic compensation effects (ACE) on SIN3A transcription.Nature communications · 2026Article
- Enhancer Dynamics for Gene Regulation in the Cardiovascular System.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Mapping cis- and trans-regulatory target genes of human-specific deletions.Nature communications · 2025Article
- A gene desert required for regulatory control of pleiotropic Shox2 expression and embryonic survival.Nature communications · 2024Article
- Multiplex profiling of developmental cis-regulatory elements with quantitative single-cell expression reporters.Nature methods · 2024Article
- Identification of ancestral gnathostome Gli3 enhancers with activity in mammals.Development, growth & differentiation · 2024Article
Corrections and comments
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Authors and funding
26 authors.
Funding
Abstract
Chromatin signatures are widely used to identify tissue-specific in vivo enhancers, but their sensitivity and specificity remains unclear. Here we show that many developmental enhancers remain undetectable using currently available chromatin data. In an initial comparison of over 1200 developmental enhancers with tissue-matched chromatin data, 14% (n = 285) lacked canonical enhancer-associated chromatin signatures. To further assess the prevalence of enhancers missed by chromatin profiling approaches, we used a high-throughput transgenic enhancer assay to screen the regulatory landscapes of two key developmental genes at 5 kb resolution, spanning 1.3 Mb of mouse sequence in total. We observed that 23 of 88 (26%) in vivo enhancers discovered by this approach lacked enhancer-associated chromatin signatures in the respective tissue. Our findings suggest the existence of tens of thousands of enhancers that remain undiscovered by currently available chromatin data, underscoring the continued need for expanding resources for enhancer discovery.
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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.