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| Status |
Public on May 21, 2020 |
| Title |
Developmentally programmed tankyrase activity upregulates β-catenin and licenses progression of embryonic genome activation |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
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.
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| Overall design |
Examination of open chromatin regions and transcription in 2-cell embryos following inhibition of tankyrase activity relative to controls.
Grant ID: 1ZIAES102985
Funding source: The Intramural Research Program of the NIH, National Institutes of Environmental Health Sciences
Title: Environmental influence on gametes and embryos
Recipient: Carmen J. Williams
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| |
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| Contributor(s) |
Gambini A, Stein P, Savy V, Grow EJ, Papas BN, Zhang Y, Kenan AC, Padilla-Banks E, Cairns BR, Williams CJ |
| Citation(s) |
32442396 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| F32 HD094500 |
Improving Bovine Cloning Efficiency by Enhancing Reprogramming during Embryonic Genome Activation (EGA) |
UNIVERSITY OF UTAH |
Edward John Grow |
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| |
| Submission date |
Dec 13, 2018 |
| Last update date |
Aug 20, 2020 |
| Contact name |
Carmen J Williams |
| E-mail(s) |
WilliamsC5@niehs.nih.gov
|
| Organization name |
NIH/NIEHS
|
| Department |
Reproductive & Developmental Biology Laboratory
|
| Street address |
111 TW Alexander Dr.
|
| City |
Research Triangle Park |
| State/province |
NC |
| ZIP/Postal code |
27709 |
| Country |
USA |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA509915 |
| SRA |
SRP173391 |
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