GABPA regulates zygotic genome activation and pluripotency formation

Mammalian early embryo development incorporates a series of processes including maternal-to-zygotic transition (MZT), zygotic genome activation (ZGA) and lineage specification etc., coupled with totipotency decline and pluripotency formation. Identification of transcription factors (TFs) orchestrating these processes remains challenging. In this study, by taking advantages of targeted protein degron system in mice, which enabled us to study TF stage-specific functions in vivo, we identified and validated the Gabpa is not only a regulator of major ZGA, but also plays an essential role in epiblast lineage specification and pluripotency formation. GABPA together with other reported pluripotency regulators plays major roles in a stepwise manner during the pluripotency formation, highlighting a dynamic multi-factorial pluripotency regulation network throughout mammalian pre-implantation development.