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

Dev Cell

State Key Laboratory of Reproductive Medicine and Offspring Health, Department of Histology and Embryology, Suzhou Affiliated Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Nanjing, China; Innovation Center of Suzhou Nanjing Medical University, Suzhou, China. Electronic address:

Published: March 2024

AI Article Synopsis

  • Zygotic genome activation (ZGA) is vital for early embryonic development, but the role of transcription factors (TFs) in this process is not well understood.
  • Researchers identified the TF KLF17 as a key player in ZGA by analyzing early mouse embryos and found that its absence negatively affects embryonic development and fertility.
  • KLF17 enhances the activation of ZGA genes by binding to their promoters and assisting in the recruitment of RNA polymerase II, which is essential for gene expression during early development.

Article Abstract

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.

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Source
http://dx.doi.org/10.1016/j.devcel.2024.01.013DOI Listing

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