PLX159764

GSE123815: Developmentally programmed tankyrase activity upregulates -catenin and licenses progression of embryonic genome activation

• Organsim mouse
• Type RNASEQ
• Target gene
• Project ARCHS4

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 -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 -catenin and promoting -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 -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 -catenin and MYC. These findings indicate that post-transcriptional regulation of tankyrase serves as a ligand-independent developmental mechanism for post-translational -catenin activation and is required to complete EGA. SOURCE: Carmen,J,Williams (WilliamsC5@niehs.nih.gov) - NIH/NIEHS