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<p>DEK is a highly conserved chromatin-associated oncoprotein that has important roles in regulating chromatin dynamics and stem cell fate. Dysregulation of DEK is associated with stem cell dysfunction and cancers, including acute myeloid leukemia. Despite its importance in chromatin regulation, the structural mechanisms underlying DEK’s interaction with chromatin and its influence on gene regulation remain poorly understood. Here we combined cryogenic electron microscopy (cryo-EM), biochemical and cellular approaches to investigate the molecular mechanisms and functional importance of DEK’s interaction with chromatin. Our cryo-EM structures reveal the structural basis of the DEK–nucleosome interaction. Biochemical and cellular results demonstrate that this interaction is crucial for DEK deposition onto chromatin. Furthermore, our results reveal that DEK safeguards mouse embryonic stem cells from acquiring primitive endoderm fates by modulating the repressive histone mark H3K27me3. Together, our study provides crucial molecular insights into the structure and function of DEK, establishing a framework for understanding its roles in chromatin biology and cell fate determination.</p>

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DEK–nucleosome structure shows DEK modulates H3K27me3 and stem cell fate

  • 期刊论文

  • 发表日期：

    2025年5月16日

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  • Yunfan Shen,
  • Yanhong Liu,
  • Maochao Guo,
  • Song Mao,
  • Rui Chen,
  • Mengran Wang,
  • Zhengbo Li,
  • Yue Li,
  • Wan Chen,
  • Fang Chen,
  • Baixing Wu,
  • Chongyuan Wang,
  • Wei Chen,
  • Huanhuan Cui,
  • Kai Yuan,
  • Hongda Huang

摘要

DEK is a highly conserved chromatin-associated oncoprotein that has important roles in regulating chromatin dynamics and stem cell fate. Dysregulation of DEK is associated with stem cell dysfunction and cancers, including acute myeloid leukemia. Despite its importance in chromatin regulation, the structural mechanisms underlying DEK’s interaction with chromatin and its influence on gene regulation remain poorly understood. Here we combined cryogenic electron microscopy (cryo-EM), biochemical and cellular approaches to investigate the molecular mechanisms and functional importance of DEK’s interaction with chromatin. Our cryo-EM structures reveal the structural basis of the DEK–nucleosome interaction. Biochemical and cellular results demonstrate that this interaction is crucial for DEK deposition onto chromatin. Furthermore, our results reveal that DEK safeguards mouse embryonic stem cells from acquiring primitive endoderm fates by modulating the repressive histone mark H3K27me3. Together, our study provides crucial molecular insights into the structure and function of DEK, establishing a framework for understanding its roles in chromatin biology and cell fate determination.