| First Author | Gambini A | Year | 2020 |
| Journal | Dev Cell | Volume | 53 |
| Issue | 5 | Pages | 545-560.e7 |
| PubMed ID | 32442396 | Mgi Jnum | J:309387 |
| Mgi Id | MGI:6754859 | Doi | 10.1016/j.devcel.2020.04.018 |
| Citation | Gambini A, et al. (2020) Developmentally Programmed Tankyrase Activity Upregulates beta-Catenin and Licenses Progression of Embryonic Genome Activation. Dev Cell 53(5):545-560.e7 |
| abstractText | 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 beta-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 beta-catenin and promoting beta-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 beta-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 beta-catenin and MYC. These findings indicate that post-transcriptional regulation of tankyrase serves as a ligand-independent developmental mechanism for post-translational beta-catenin activation and is required to complete EGA. |
