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<p>The nucleolus, a membrane-less organelle essential for ribosome biogenesis, adopts variable shapes across cell types and in response to environmental conditions, yet the mechanisms regulating its morphology and functional implications remain unclear. Using a high-throughput screen, we identify the proliferation marker Ki-67 as a central regulator of nucleolar shape. Ki-67 localises to the chromatin-nucleolus interface, where its depletion induces nucleolar rounding and reduces chromatin enrichment both at the nucleolar rim and within internal invaginations. This effect is driven by Ki-67’s amphiphilic properties conferred by two distinct affinity domains separated by a spacer. Given that chromatin loss is a common feature of rounded nucleoli in our screen, and acute chromatin digestion also induces rounding, we propose that the chromatin environment in and around the nucleolus plays a key role in determining nucleolar shape. Our study elucidates a novel Ki-67-mediated chromatin anchoring mechanism, tightly linking nucleolar shape to genome organisation and expanding our understanding of condensate morphology.</p>

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Ki-67 shapes the nucleolus by anchoring chromatin via its amphiphilic properties

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月24日

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  • Daja Schichler,
  • Yuki Hayashi,
  • Letitia Fernandez,
  • Mariam Chupanova,
  • Alberto Hernandez-Armendariz,
  • Beate Neumann,
  • Sara Cuylen-Haering

摘要

The nucleolus, a membrane-less organelle essential for ribosome biogenesis, adopts variable shapes across cell types and in response to environmental conditions, yet the mechanisms regulating its morphology and functional implications remain unclear. Using a high-throughput screen, we identify the proliferation marker Ki-67 as a central regulator of nucleolar shape. Ki-67 localises to the chromatin-nucleolus interface, where its depletion induces nucleolar rounding and reduces chromatin enrichment both at the nucleolar rim and within internal invaginations. This effect is driven by Ki-67’s amphiphilic properties conferred by two distinct affinity domains separated by a spacer. Given that chromatin loss is a common feature of rounded nucleoli in our screen, and acute chromatin digestion also induces rounding, we propose that the chromatin environment in and around the nucleolus plays a key role in determining nucleolar shape. Our study elucidates a novel Ki-67-mediated chromatin anchoring mechanism, tightly linking nucleolar shape to genome organisation and expanding our understanding of condensate morphology.