Embryonic genome activation (EGA) is orchestrated by an intrinsic developmental program initiated during oocyte maturation with translation of stored maternal mRNAs. Here, we show that tankyrase, a poly(ADP-ribosyl) polymerase that regulates β-catenin levels, undergoes programmed translation during oocyte maturation and serves an essential role in mouse EGA. Newly translated TNKS triggers proteasomal degradation of axin, reducing targeted destruction of β-catenin and promoting β-catenin-mediated transcription of target genes, including Myc. MYC mediates ribosomal RNA transcription in 2-cell embryos, supporting global protein synthesis. Suppression of tankyrase activity using knockdown or chemical inhibition causes loss of nuclear β-catenin and global reductions in transcription and histone H3 acetylation. Chromatin and transcriptional profiling indicate that development arrests prior to the mid-2-cell stage, mediated in part by reductions in β-catenin and MYC. These findings indicate that post-transcriptional regulation of tankyrase serves as a ligand-independent developmental mechanism for post-translational β-catenin activation and is required to complete EGA.

胚胎基因组激活（EGA）通过在卵母细胞成熟过程中启动的内在发育程序进行编排，该程序具有存储的母体mRNA的翻译功能。在这里，我们表明，tankyrase，一种调节β-catenin水平的聚（ADP-核糖基）聚合酶，在卵母细胞成熟过程中经历程序翻译，并在小鼠EGA中起重要作用。新翻译的TNKS触发蛋白酶的蛋白酶降解，减少针对性的β-catenin破坏并促进β-catenin介导的目标基因（包括Myc）的转录。MYC介导2细胞胚胎中的核糖体RNA转录，支持整体蛋白质合成。使用敲除或化学抑制作用抑制坦科聚合酶活性会导致核β-连环蛋白的损失以及转录和组蛋白H3乙酰化的整体降低。染色质和转录谱表明，发育停滞在2细胞中期之前，部分是由β-连环蛋白和MYC的减少介导的。这些发现表明，端锚聚合酶的转录后调节充当翻译后β-连环蛋白激活的非配体依赖性发育机制，并且是完成EGA所必需的。