Scientific article
OA Policy
English

Temporal constraints on enhancer usage shape the regulation of limb gene transcription

Published inNature communications, vol. 17, no. 1, 5
First online date2026-01-12
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.

Keywords
  • Animals
  • Enhancer Elements, Genetic / genetics
  • Extremities / embryology
  • Gene Expression Regulation, Developmental
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Mice
  • Mice, Transgenic
  • Promoter Regions, Genetic / genetics
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription, Genetic
Citation (ISO format)
ROUCO, Raquel et al. Temporal constraints on enhancer usage shape the regulation of limb gene transcription. In: Nature communications, 2026, vol. 17, n° 1, p. 5. doi: 10.1038/s41467-025-66055-6
Main files (1)
Article (Published version)
Secondary files (12)
Supplemental data
accessLevelPublic
Supplemental data
accessLevelPublic
Supplemental data
accessLevelPublic
Show more
Identifiers
Additional URL for this publicationhttps://www.nature.com/articles/s41467-025-66055-6
Journal ISSN2041-1723
40views
24downloads

Technical informations

Creation13/01/2026 01:33:51
First validation15/01/2026 15:45:09
Update15/01/2026 15:45:09
Status update15/01/2026 15:45:09
Last indexation15/01/2026 15:45:10
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack