Ubiquitin-proteasome system modulates zygotic genome activation in early mouse embryos and influences full-term development

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  • HIGUCHI Chika
    Laboratory of Molecular Developmental Biology, Graduate School of Biology-Oriented Science and Technology, Kindai University, Wakayama 649-6493, Japan
  • SHIMIZU Natsumi
    Laboratory for Organismal Patterning, RIKEN Center for Developmental Biology, Hyogo 650-0047, Japan
  • SHIN Seung-Wook
    Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Maryland 20892, USA
  • MORITA Kohtaro
    Laboratory of Molecular Developmental Biology, Graduate School of Biology-Oriented Science and Technology, Kindai University, Wakayama 649-6493, Japan
  • NAGAI Kouhei
    Laboratory of Molecular Developmental Biology, Graduate School of Biology-Oriented Science and Technology, Kindai University, Wakayama 649-6493, Japan
  • ANZAI Masayuki
    Laboratory of Molecular Developmental Biology, Graduate School of Biology-Oriented Science and Technology, Kindai University, Wakayama 649-6493, Japan Institute of Advanced Technology, Kindai University, Wakayama 642-0017, Japan
  • KATO Hiromi
    Laboratory of Molecular Developmental Biology, Graduate School of Biology-Oriented Science and Technology, Kindai University, Wakayama 649-6493, Japan Institute of Advanced Technology, Kindai University, Wakayama 642-0017, Japan
  • MITANI Tasuku
    Laboratory of Molecular Developmental Biology, Graduate School of Biology-Oriented Science and Technology, Kindai University, Wakayama 649-6493, Japan Institute of Advanced Technology, Kindai University, Wakayama 642-0017, Japan
  • YAMAGATA Kazuo
    Laboratory of Molecular Developmental Biology, Graduate School of Biology-Oriented Science and Technology, Kindai University, Wakayama 649-6493, Japan
  • HOSOI Yoshihiko
    Laboratory of Molecular Developmental Biology, Graduate School of Biology-Oriented Science and Technology, Kindai University, Wakayama 649-6493, Japan
  • MIYAMOTO Kei
    Laboratory of Molecular Developmental Biology, Graduate School of Biology-Oriented Science and Technology, Kindai University, Wakayama 649-6493, Japan
  • MATSUMOTO Kazuya
    Laboratory of Molecular Developmental Biology, Graduate School of Biology-Oriented Science and Technology, Kindai University, Wakayama 649-6493, Japan

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Abstract

<p> Maternal RNA/protein degradation and zygotic genome activation (ZGA), occurring during maternal-to-zygotic transition (MZT), are the first essential events for the development of pre-implantation embryos. Previously, we have shown the importance of the ubiquitin-proteasome system (UPS) for initiation of minor ZGA at the 1-cell stage of mouse embryos. However, little is known about the mechanism of involvement of the UPS-degraded maternal proteins in ZGA. In this study, we investigated the effect of inhibiting maternal protein degradation by the reversible proteasome inhibitor, MG132, on post-implantation development and ZGA regulation during early cleavage stages. Our study revealed that zygotic transcription by RNA polymerase II (Pol II) at the 1-cell stage was delayed and the full-term development was affected by transient proteasome inhibition during 1 to 9 h post-insemination (hpi). Furthermore, we found that the transient inhibition of proteasome activity at the 2-cell stage delayed the onset of transcription of some major ZGA genes. These results support the model hypothesizing the requirement of sequential degradation of maternal proteins by UPS for the proper onset of ZGA and normal progression of MZT in early mouse embryos.</p>

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