Maternal KLF17 controls zygotic genome activation by acting as a messenger for RNA Pol II recruitment in mouse embryos.

Initiation of timely and sufficient zygotic genome activation (ZGA) is crucial for the beginning of life, yet our knowledge of transcription factors (TFs) contributing to ZGA remains limited. Here, we screened the proteome of early mouse embryos after cycloheximide (CHX) treatment and identified maternally derived KLF17 as a potential TF for ZGA genes. Using a conditional knockout (cKO) mouse model, we further investigated the role of maternal KLF17 and found that it promotes embryonic development and full fertility. Mechanistically, KLF17 preferentially binds to promoters and recruits RNA polymerase II (RNA Pol II) in early 2-cell embryos, facilitating the expression of major ZGA genes. Maternal Klf17 knockout resulted in a downregulation of 9% of ZGA genes and aberrant RNA Pol II pre-configuration, which could be partially rescued by introducing exogenous KLF17. Overall, our study provides a strategy for screening essential ZGA factors and identifies KLF17 as a crucial TF in this process. [Display omitted] • Maternal transcription complexes are translationally activated before major ZGA • KLF17 is maternally required for preimplantation development and female fertility • Maternal KLF17 guides RNA Pol II to promote timely ZGA initiation • Maternal KLF17 participates in RNA Pol II pre-configuration Hu et al. identify KLF17 as a crucial player in early embryonic development through proteomic analysis in mice, showcasing its involvement in major ZGA. They highlight the importance of KLF17 as an independent regulatory factor, actively participating in RNA Pol II pre-configuration and exerting maternal effects. [ABSTRACT FROM AUTHOR]