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<p>The initiation of gene expression during development, known as zygotic genome activation (ZGA), is accompanied by massive changes in chromosome organization. However, the earliest events of chromosome folding and their functional roles remain unclear. Using Hi-C on zebrafish embryos, we discovered that chromosome folding begins early in development with the formation of fountains, distinct elements of chromosome organization. Emerging preferentially at enhancers, fountains show an initial accumulation of cohesin, which later redistributes to CTCF sites at TAD borders. Knockouts of pioneer transcription factors driving ZGA enhancers cause a specific loss of fountains, establishing a causal link between enhancer activation and fountain formation. Polymer simulations demonstrate that fountains may arise as sites of facilitated cohesin loading, requiring two-sided but desynchronized loop extrusion, potentially caused by cohesin collisions with obstacles or internal switching. Moreover, we detected cohesin-dependent fountain patterns at enhancers in mouse cells and found them reemerging with cohesin loading after mitosis. Altogether, fountains represent enhancer-specific elements of chromosome organization and suggest that chromosome folding during development and after cell division starts with facilitated cohesin loading. Observations in multiple systems further support facilitated loading at enhancers as a widespread phenomenon.</p>

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Extrusion fountains are hallmarks of chromosome organization emerging upon zygotic genome activation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月14日

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  • Aleksandra Galitsyna,
  • Sergey V. Ulianov,
  • Mariia Bazarevich,
  • Nikolai S. Bykov,
  • Marina Veil,
  • Meijiang Gao,
  • Kristina Perevoschikova,
  • Mikhail S. Gelfand,
  • Sergey V. Razin,
  • Leonid Mirny,
  • Daria Onichtchouk

摘要

The initiation of gene expression during development, known as zygotic genome activation (ZGA), is accompanied by massive changes in chromosome organization. However, the earliest events of chromosome folding and their functional roles remain unclear. Using Hi-C on zebrafish embryos, we discovered that chromosome folding begins early in development with the formation of fountains, distinct elements of chromosome organization. Emerging preferentially at enhancers, fountains show an initial accumulation of cohesin, which later redistributes to CTCF sites at TAD borders. Knockouts of pioneer transcription factors driving ZGA enhancers cause a specific loss of fountains, establishing a causal link between enhancer activation and fountain formation. Polymer simulations demonstrate that fountains may arise as sites of facilitated cohesin loading, requiring two-sided but desynchronized loop extrusion, potentially caused by cohesin collisions with obstacles or internal switching. Moreover, we detected cohesin-dependent fountain patterns at enhancers in mouse cells and found them reemerging with cohesin loading after mitosis. Altogether, fountains represent enhancer-specific elements of chromosome organization and suggest that chromosome folding during development and after cell division starts with facilitated cohesin loading. Observations in multiple systems further support facilitated loading at enhancers as a widespread phenomenon.