Germ-cell specific eIF4E1B regulates maternal RNA translation to ensure zygotic genome activation

Abstract Translation of maternal mRNAs is detected before transcription of zygotic genes and is essential for mammalian embryo development. How certain maternal mRNAs are selected for translation instead of degradation and how this burst of translation affects zygotic genome activation remains unknown. Using gene-edited mice, we document that the eukaryotic translation initiation factor 4E family member 1B (eIF4E1B) is the regulator of maternal mRNA translation that ensures subsequent reprogramming of the zygotic genome. In oocytes, the germ-cell specific eIF4E1B binds to mRNAs encoding chromatin remodeling complexes as well as reprogramming factors to protect them from degradation and promote their translation in zygotes. These protein products establish an open chromatin landscape in one-cell zygotes and enable transcription. Our results define a program for rapid resetting of the zygotic epigenome that is regulated by maternal mRNA translation and provides new insight into the mammalian maternal-to-zygotic transition.