Scholarlink

<p>Transcription factors (TFs) are instrumental in kickstarting embryonic genome activation (EGA) in many species, yet their regulatory roles in human embryos remain poorly understood. Here, we show that OTX2, a maternally provided PRD-like homeobox TF, is required for proper human EGA and early development. At the four-cell stage, OTX2 promotes activation of key EGA genes, including <i>TPRX1</i> and <i>TPRX2</i>, and the EGA-associated repeat HERVL-int and MLT2A1. At EGA targets, OTX2 directly binds promoters and putative enhancers, many of which overlap with Alu and MaLR repetitive elements containing the OTX2 motif, and promotes chromatin accessibility. The transcriptome and developmental defects upon <i>OTX2</i> knockdown are partially rescued by overexpression of <i>TPRX1</i> and <i>TPRX2</i>. Finally, joint knockdown of <i>OTX2</i> and <i>TPRXL</i>, encoding another maternal PRD-like homeobox TF, exacerbates chromatin opening and EGA defects at the 8C stage. These findings establish OTX2 as a crucial maternal TF that awakes the genome at the beginning of human life.</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

Maternal factor OTX2 regulates human embryonic genome activation and early development

  • 期刊论文

  • 发表日期：

    2025年10月27日

查看全文
  • Qiuyan Wang,
  • Chuanxin Zhang,
  • Yanna Dang,
  • Jiaqi Sun,
  • Zhuoning Zou,
  • Cheng Li,
  • Shuiying Ma,
  • Zongyu Li,
  • Hui Liu,
  • Xiaonan Ma,
  • Zhen Yang,
  • Lijuan Wang,
  • Keliang Wu,
  • Zi-Jiang Chen,
  • Wei Xie,
  • Han Zhao

摘要

Transcription factors (TFs) are instrumental in kickstarting embryonic genome activation (EGA) in many species, yet their regulatory roles in human embryos remain poorly understood. Here, we show that OTX2, a maternally provided PRD-like homeobox TF, is required for proper human EGA and early development. At the four-cell stage, OTX2 promotes activation of key EGA genes, including TPRX1 and TPRX2, and the EGA-associated repeat HERVL-int and MLT2A1. At EGA targets, OTX2 directly binds promoters and putative enhancers, many of which overlap with Alu and MaLR repetitive elements containing the OTX2 motif, and promotes chromatin accessibility. The transcriptome and developmental defects upon OTX2 knockdown are partially rescued by overexpression of TPRX1 and TPRX2. Finally, joint knockdown of OTX2 and TPRXL, encoding another maternal PRD-like homeobox TF, exacerbates chromatin opening and EGA defects at the 8C stage. These findings establish OTX2 as a crucial maternal TF that awakes the genome at the beginning of human life.