The article details the critical role of the maternal transcription factor OTX2 in regulating the initiation of life through human embryonic genome activation (EGA). The research demonstrates that OTX2 is essential for minor EGA at the four-cell stage, promoting the activation of key genes like TPRX1 and TPRX2 and increasing chromatin accessibility by binding to repetitive elements like Alu and MaLR. Experimental depletion of OTX2 resulted in developmental and gene expression defects, which were partially rescued by the overexpression of its downstream targets, TPRX1 and TPRX2. Furthermore, OTX2 works redundantly with another maternal factor, TPRXL, to jointly regulate gene activation and chromatin accessibility during the subsequent major EGA at the eight-cell stage, establishing a hierarchical regulatory circuit for early human development.

References:

• Wang Q, Zhang C, Dang Y, et al. Maternal factor OTX2 regulates human embryonic genome activation and early development[J]. Nature Genetics, 2025: 1-13.