Scholarlink

<p>The cell-type-specific function of transcription factors (TFs) is crucial for determining cellular identity. However, it is unclear how a single TF can function specifically in different cell types. Here, we define the molecular features that enable OCT4 to reprogram somatic cells into pluripotent or trophoblast stem cells, maintain the self-renewal of embryonic stem cells (ESCs), and drive lineage commitment during early embryonic development. Embedded within the intrinsically disordered regions (IDRs) of OCT4, we uncover <Emphasis Type="Underline">s</Emphasis>hort <Emphasis Type="Underline">li</Emphasis>near <Emphasis Type="Underline">p</Emphasis>eptides that are <Emphasis Type="Underline">e</Emphasis>ssential for <Emphasis Type="Underline">r</Emphasis>eprogramming (SLiPERs) but dispensable for ESC self-renewal. SLiPERs adopt a quasi-ordered state and, during reprogramming, recruit a unique set of proteins to closed chromatin that are unnecessary for ESC self-renewal. Interestingly, SLiPERs are essential for embryos to develop beyond late gastrulation. Removing SLiPERs leads to aberrant OCT4 binding, derailing the regular transition of ESCs out of pluripotency. Our findings identify modules within IDRs that contribute to the functional versatility and specificity of TFs.</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

Cell-type-specific functionality encoded within the intrinsically disordered regions of OCT4

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年9月30日

查看全文
  • Burak Ozkan,
  • Mitzy Rios de Anda,
  • Elisa Hall-Ponsele,
  • Maria Rosa Portero Migueles,
  • Amani Alshaikh,
  • Marta Hanzevacki,
  • Moriyah Naama,
  • Katharine Furlong,
  • Gareth A. Roberts,
  • Meryam Beniazza,
  • My Linh Huynh,
  • Michael R. O’Dwyer,
  • Sonia Yiakoumi,
  • Christos Spanos,
  • Hazar Yassen,
  • Keisuke Kaji,
  • Hitoshi Niwa,
  • Yosef Buganim,
  • Sally Lowell,
  • Abdenour Soufi

摘要

The cell-type-specific function of transcription factors (TFs) is crucial for determining cellular identity. However, it is unclear how a single TF can function specifically in different cell types. Here, we define the molecular features that enable OCT4 to reprogram somatic cells into pluripotent or trophoblast stem cells, maintain the self-renewal of embryonic stem cells (ESCs), and drive lineage commitment during early embryonic development. Embedded within the intrinsically disordered regions (IDRs) of OCT4, we uncover short linear peptides that are essential for reprogramming (SLiPERs) but dispensable for ESC self-renewal. SLiPERs adopt a quasi-ordered state and, during reprogramming, recruit a unique set of proteins to closed chromatin that are unnecessary for ESC self-renewal. Interestingly, SLiPERs are essential for embryos to develop beyond late gastrulation. Removing SLiPERs leads to aberrant OCT4 binding, derailing the regular transition of ESCs out of pluripotency. Our findings identify modules within IDRs that contribute to the functional versatility and specificity of TFs.