Dppa2 Promotes Early Embryo Development Through Regulating PDH Expression Pattern During Zygotic Genome Activation

During embryonic development, zygotic genome activation (ZGA) is a critical event that determines the rational process and the fate of embryonic cells. The tricarboxylic acid cycle (TCA cycle) provides necessary reactants and energy for biological activities such as genome activation, chromatin opening, and epigenetic modifications during ZGA. Recent studies have shown that during ZGA, core enzymes associated with TCA briefly enter the nucleus and participate in initiating the ZGA process. However, the regulatory relationship between ZGA factors, such as Dux, Dppa2, and Dppa4, and the core enzymes of the TCA cycle remains unknown. In this study, we found that Dppa2 plays a key role in ZGA by directly determining the localization of TCA core enzymes, thereby affecting the early embryonic development. To further investigate the effect of Dppa2 on the localization of pyruvate dehydrogenase (PDH), we followed the establishment of an inducible Dppa2 transgenic mouse model. We found that the "chronoectopic" expression of Dppa2 prior to normal ZGA time could lead to the advanced nuclear localization of PDH. In summary, Dppa2 plays a key role in ZGA, directly determining the location of TCA core enzymes in early embryos. This study provides a theoretical basis for early embryonic development at the metabolic regulation level.