2025年10月27日，山东大学赵涵课题组在《自然—遗传学》杂志发表论文，宣布他们探明了母体因子OTX2调控人类胚胎基因组激活和早期发育。

该课题组人员发现OTX2，一种母体提供的类似PRD的同源盒TF，是人类正常EGA和早期发育所必需的。在前细胞阶段，OTX2促进关键EGA基因的激活，包括TPRX1和TPRX2，以及EGA相关的重复序列HERVL-int和MLT2A1。在EGA靶点，OTX2直接结合启动子和假定的增强子，其中许多与含有OTX2基序的Alu和MaLR重复元件重叠，并促进染色质的可及性。TPRX1和TPRX2的过表达部分修复了OTX2敲低后的转录组和发育缺陷。最后，编码另一个母体PRD样同源盒TF的OTX2和TPRXL的联合敲低加剧了8C期染色质开放和EGA缺陷。这些发现证实了OTX2是一个重要的母体TF，在人类生命开始时唤醒基因组。

据介绍，在许多物种中，转录因子（TFs）在启动胚胎基因组激活（EGA）方面发挥着重要作用，但它们在人类胚胎中的调节作用仍然知之甚少。

附：英文原文

Title: Maternal factor OTX2 regulates human embryonic genome activation and early development

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

Issue&Volume: 2025-10-27

Abstract: 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.

DOI: 10.1038/s41588-025-02350-8

Source: https://www.nature.com/articles/s41588-025-02350-8