Maternal factor OTX2 regulates human zygotic genome activation and early development
Release date:
2025-07-18
Description:
Zygotic Genome Activation (ZGA), the first transcription event in life, awakens the dormant genome and initiates the embryonic program to start the maternal-to-zygotic transition. Pre-existing maternal transcription factors (TFs) presumably are instrumental in kickstarting ZGA. How TFs regulate human ZGA in early embryos remains largely unknown. OTX2, a maternal PRD-like homeobox domain TF, is highly activated for its translation prior to human ZGA. By depleting OTX2 in human embryos, we found OTX2 is required for proper minor ZGA and early human development. This is achieved in part by binding and opening chromatin near ZGA genes. Finally, joint knockdown of OTX2 and TPRXL, the two major maternal PRD-like homeobox TFs, exacerbates inefficient chromatin opening, major ZGA defects and results in severe developmental abnormalities. These findings underscore a crucial role of maternal TFs in regulating human ZGA and early development.
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Submitter: Xie Wei / xiewei121@tsinghua.edu.cn
Organization: Tsinghua University
Submission date: 2024-01-31
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