ArticleNature communications2026
Temporal constraints on enhancer usage shape the regulation of limb gene transcription.
Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Temporal loss ofGenes & development · 2026Article
- DNA methylation profiles aid to identify putative genome activation histories along lymphomagenesis.NAR genomics and bioinformatics · 2026Article
- Temporal constraints on enhancer usage shape the regulation of limb gene transcription.Nature communications · 2026Article
- Linking shox/shox2 deficiency with fgfr3 gain-of-function and natriuretic peptides.Frontiers in endocrinology · 2026Article
- Specialized signaling centers direct cell fate and spatial organization in a mesodermal organoid model.Science advances · 2025Article
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Authors and funding
7 authors.
Funding
Abstract
Enhancer repertoires orchestrate gene expression during embryonic development, shaping organ structure and function. Individual enhancers can act in overlapping or distinct spatial domains, but their temporal specificity and coordinated action over time remain poorly understood. Here, we identify temporally restricted enhancer repertoires at multiple loci involved in mouse limb development. To capture their dynamic roles, we introduce the regulatory trajectory framework comprising initiation, maintenance, and decommissioning of gene expression. Using a transgenic recorder at the Shox2 locus, we demonstrate that early enhancers initiate transcription, while late enhancers maintain it. Additionally, we found that changes in 3D topology associate with enhancer activities and that loss of enhancer-promoter contacts occurs during decommissioning. Finally, we show that Shox2 regulatory decommissioning can be driven by Hoxd13, a known antagonist of Shox2 expression. Overall, our work uncovers how temporally restricted enhancers generate complex expression patterns and sheds light on the dynamics of enhancer-promoter interactions.
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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 Socratic graph.