Scholarlink

<p>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 candidate EEs (cEEs) 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 cEEs in the cis-regulation of host and distal gene expression. Through large-scale cancer genome analyses, we reveal that cEE mutations correlate with dysregulated target-gene expression and clinical outcomes, highlighting their potential relevance in disease. Evolutionary comparisons show that cEEs exhibit both strong sequence constraint and lineage-specific plasticity, suggesting that they serve ancient regulatory functions while also contributing to species divergence. Our findings expand the landscape of functional elements by establishing cEEs as a component of gene regulation, while revealing how coding regions can simultaneously fulfil both protein-coding and cis-regulatory roles.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月2日

查看全文
  • Jean-Christophe Mouren,
  • Magali Torres,
  • Antoinette van Ouwerkerk,
  • Iris Manosalva,
  • Frederic Gallardo,
  • Salvatore Spicuglia,
  • Benoit Ballester

摘要

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 candidate EEs (cEEs) 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 cEEs in the cis-regulation of host and distal gene expression. Through large-scale cancer genome analyses, we reveal that cEE mutations correlate with dysregulated target-gene expression and clinical outcomes, highlighting their potential relevance in disease. Evolutionary comparisons show that cEEs exhibit both strong sequence constraint and lineage-specific plasticity, suggesting that they serve ancient regulatory functions while also contributing to species divergence. Our findings expand the landscape of functional elements by establishing cEEs as a component of gene regulation, while revealing how coding regions can simultaneously fulfil both protein-coding and cis-regulatory roles.