Scholarlink

<p>Topologically associating domains (TADs) and chromatin architectural loops impact promoter–enhancer interactions, with CCCTC-binding factor (CTCF) defining TAD borders and loop anchors. TAD boundaries and loops progressively strengthen upon embryonic stem (ES) cell differentiation, underscoring the importance of chromatin topology in ontogeny. However, the mechanisms driving this process remain unclear. Here we show a widespread increase in CTCF–RNA-binding protein (RBP) interactions upon ES to neural stem (NS) cell differentiation. While dispensable in ES cells, RBPs reinforce CTCF-anchored chromatin topology in NS cells. We identify Pantr1, a non-coding RNA, as a key facilitator of CTCF–RBP interactions, promoting chromatin maturation. Using acute CTCF degradation, we find that, through its insulator function, CTCF helps maintain neuronal gene silencing in NS cells by acting as a barrier to untimely gene activation during development. Altogether, we reveal a fundamental mechanism driving developmentally linked chromatin structural consolidation and the contribution of this process to the control of gene expression in differentiation.</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

RNA-binding proteins mediate the maturation of chromatin topology during differentiation

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年9月8日

查看全文
  • Bondita Dehingia,
  • Małgorzata Milewska-Puchała,
  • Marcin Janowski,
  • Mahmoud-Reza Rafiee,
  • Misbah Abbas,
  • Aleksandra Piotrowska,
  • Jan Senge,
  • Piotr Blaut,
  • Dietrich Walsh,
  • Jacqueline Severino,
  • Debadeep Chaudhury,
  • Sajjad Iqbal,
  • Rogelio Montiel-Manriquez,
  • Sylwia Jankowska,
  • Peyman Zare,
  • Wolfgang Huber,
  • Jianliang Xu,
  • Rafael Casellas,
  • Timo Zimmermann,
  • Paweł Dłotko,
  • Jeroen Krijgsveld,
  • Aleksandra Pękowska

摘要

Topologically associating domains (TADs) and chromatin architectural loops impact promoter–enhancer interactions, with CCCTC-binding factor (CTCF) defining TAD borders and loop anchors. TAD boundaries and loops progressively strengthen upon embryonic stem (ES) cell differentiation, underscoring the importance of chromatin topology in ontogeny. However, the mechanisms driving this process remain unclear. Here we show a widespread increase in CTCF–RNA-binding protein (RBP) interactions upon ES to neural stem (NS) cell differentiation. While dispensable in ES cells, RBPs reinforce CTCF-anchored chromatin topology in NS cells. We identify Pantr1, a non-coding RNA, as a key facilitator of CTCF–RBP interactions, promoting chromatin maturation. Using acute CTCF degradation, we find that, through its insulator function, CTCF helps maintain neuronal gene silencing in NS cells by acting as a barrier to untimely gene activation during development. Altogether, we reveal a fundamental mechanism driving developmentally linked chromatin structural consolidation and the contribution of this process to the control of gene expression in differentiation.