Stat3 is a upstream regulator of Granzyme g that triggers the minor zygotic gene activation in mouse preimplantation embryo

Abstract

Maternal zygotic transition (MZT) that control from maternal massage to zygotic gene activation (ZGA) promote preimplantation embryo development in mouse 1‐ to 2‐cell stage. Mouse Granzyme g (Gzmg) is an important protease and specificity expressed at 2‐cell stage of mouse embryos. In our previous report, we found that zygotic RNA synthesize is blocked in Gzmg knock‐down 2‐cell embryo. These data indicated that Gzmg is a necessary protein in MZT. Recently, we found the −417 ~ +28 nt upstream sequence of Gzmg gene may contain cis‐elements to regulate Gzmg expression pattern in mouse zygote and 2‐cell stages by promoter assay in mouse preimplantation embryos. Furthermore, we predicted transcription factor binding sites in promoter sequence by JASPAR and expression atlas website. Gabpa and Stat3 were selected by comparing promoter assay and JASPAR website. These two transcription factors were located in zygote and 2‐cell embryo's nuclei by immunofluorescence. These data supposed that Gabpa and Stat3 may have transcriptional activity to regulate genes in zygote and 2‐cell stages. Surprisingly, the Stat3 can be accumulated in mouse zygote and 2‐cell nuclei by injecting −417~+28 nt upstream sequence of Gzmg into zygote and 2‐cell nuclei. These data indicated that Stat3 is a maternal transcription factor and may regulate Gzmg to promote MZT. Thus, we used inhibitor treatment to define timing of embryo development affected by Stat3. After treatment with S3I‐201, Stat3 inhibitor, mouse embryos were arrested at zygote and 2‐cell stages and some of embryos were arrested at 2‐cell when treated with another inhibitor, WP1066. These results suggest that Stat3 may play important roles at zygote and 2‐cell stages. Take together, Stat3 may promote mouse preimplantation embryo development by triggering the minor ZGA and activating Gzmg gene.