MYC is essential for induction of major ZGA and subsequent preimplantation development

In mouse preimplantation development, zygotic genome activation (ZGA), which synthesizes new transcripts from the embryos, begins in the S phase of the one-cell stage, with major ZGA occurring especially at the late two-cell stage. Myc is a transcription factor expressed in parallel with ZGA, but its direct association with the major ZGA has not been clarified. In this study, we found that developmental arrest occurs at the two-cell stage when mouse embryos were treated with antisense oligos targeting Myc or inhibitors specific for MYC from the one-cell stage. In order to identify when MYC inhibition affected development, we applied time-limited inhibitor treatment, and found that inhibition of MYC at the two-cell, four-cell, and morula stages had no effect on preimplantation development, whereas treatment with the inhibitor at the early two-cell stage arrested development at the two-cell stage. Furthermore, transcriptome analysis revealed that when MYC function was inhibited, genes expressed in the major ZGA phase were suppressed. These results suggest that Myc is essential for the induction of major ZGA and its subsequent development. Revealing the function of Myc in preimplantation development is expected to contribute to advances in assisted reproductive technology.