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<p>Transcriptional enhancers must locate target genes with precision. In mammals, topologically associating domains (TADs) guide this process, but the <i>C. elegans</i> genome lacks such organization despite containing over 30,000 putative enhancers. Using high-resolution Hi-C, we identify distinct 3D chromatin structures around active enhancers, termed fountains. These ~38 kb cohesin-dependent structures are unique to active enhancers and enriched for topoisomerases and negatively supercoiled DNA, indicating topological stress. Disrupting cohesin collapses fountains and leads to transcriptional upregulation of nearby genes, suggesting fountains act as spatial repressors controlling enhancer–promoter communication. This repression preferentially affects neuronal genes, including <i>skn-1/Nrf</i>, which changes isoform usage upon cohesin loss in ASI neurons. Cohesin cleavage also alters nematode movement and foraging behavior, linking 3D genome architecture to neural function and behavior. Thus, fountains represent a distinctive chromatin feature that may ensure enhancer specificity in a TAD-less genome.</p>

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Cohesin forms fountains at active enhancers in C. elegans

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月11日

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  • Bolaji N. Lüthi,
  • Jennifer I. Semple,
  • Anja Haemmerli,
  • Saurabh Thapliyal,
  • Kalyan Ghadage,
  • Klement Stojanovski,
  • Dario D’Asaro,
  • Moushumi Das,
  • Nick Gilbert,
  • Dominique A. Glauser,
  • Benjamin Towbin,
  • Daniel Jost,
  • Peter Meister

摘要

Transcriptional enhancers must locate target genes with precision. In mammals, topologically associating domains (TADs) guide this process, but the C. elegans genome lacks such organization despite containing over 30,000 putative enhancers. Using high-resolution Hi-C, we identify distinct 3D chromatin structures around active enhancers, termed fountains. These ~38 kb cohesin-dependent structures are unique to active enhancers and enriched for topoisomerases and negatively supercoiled DNA, indicating topological stress. Disrupting cohesin collapses fountains and leads to transcriptional upregulation of nearby genes, suggesting fountains act as spatial repressors controlling enhancer–promoter communication. This repression preferentially affects neuronal genes, including skn-1/Nrf, which changes isoform usage upon cohesin loss in ASI neurons. Cohesin cleavage also alters nematode movement and foraging behavior, linking 3D genome architecture to neural function and behavior. Thus, fountains represent a distinctive chromatin feature that may ensure enhancer specificity in a TAD-less genome.