Article Dans Une Revue Nature Communications Année : 2026

Exonic enhancers are a widespread class of dual-function regulatory elements

Résumé

Exonic enhancers (EEs) occupy an under-appreciated niche in gene regulation. By integrating transcription factor binding, chromatin accessibility, and high-throughput enhancer-reporter assays, we demonstrate that many protein-coding exons possess enhancer activity across species. These EEs exhibit characteristic epigenomic signatures, form long-range interactions with gene promoters, and can be altered by both nonsynonymous and synonymous variants. CRISPR–mediated inactivation demonstrated the involvement of EEs in the cis-regulation of host and distal gene expression. Through large-scale cancer genome analyses, we reveal that EE mutations correlate with dysregulated target-gene expression and clinical outcomes, highlighting their potential relevance in disease. Evolutionary comparisons show that EEs exhibit both strong sequence constraint and lineage-specific plasticity, suggesting that they serve ancient regulatory functions while also contributing to species divergence. Our findings redefine the landscape of functional elements by establishing EEs as a component of gene regulation, while revealing how coding regions can simultaneously fulfil both protein-coding and cis-regulatory roles.

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hal-05126239 , version 1 (10-04-2026)

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Jean-Christophe Mouren, Magali Torres, Antoinette van Ouwerkerk, Iris Manosalva, Frederic Gallardo, et al.. Exonic enhancers are a widespread class of dual-function regulatory elements. Nature Communications, 2026, ⟨10.1038/s41467-026-71220-6⟩. ⟨hal-05126239⟩

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