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| Status |
Public on Jun 23, 2023 |
| Title |
Maternal TDP-43 interacts with RNA Pol II and regulates zygotic genome activation |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Other
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| Summary |
Zygotic genome activation (ZGA) is essential for early embryonic development. However, the regulation of ZGA remains elusive in mammals. Here we report that a maternal factor TDP-43, a nuclear transactive response DNA-binding protein, regulates ZGA through RNA Pol II and is essential for mouse early embryogenesis. Maternal TDP-43 translocates from the cytoplasm into the nucleus at the early two-cell stage when minor to major ZGA transition occurs. Genetic deletion of maternal TDP-43 results in mouse early embryos arrested at late two-cell stage and female infertile. TDP-43 co-occupies with RNA Pol II as large foci in the nucleus and also at the promoters of ZGA genes at the late two-cell stage. Biochemical evidence indicates that TDP-43 binds Polr2a and Cyclin T1. Depletion of maternal TDP-43 caused the loss of Pol II foci and reduced Pol II binding on chromatin at major ZGA genes, accompanied by defective ZGA. Collectively, our results suggest that maternal TDP-43 is critical for mouse early embryonic development, in part through facilitating the correct RNA Pol II configuration and zygotic genome activation.
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| Overall design |
RNA-seq experiments were performed in WT and TDP-43 knockout mouse oocytes, one-cell and two-cell embryos.Stacc-seq experiments were applied to WT FGO and embryos with the antibodies against Pol II or TDP43 and to TDP-43 knockout two-cell embryos with the Pol II antibody.
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| Web link |
https://www.nature.com/articles/s41467-023-39924-1
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| Contributor(s) |
Nie X, Xu Q, Chen F, Li L |
| Citation(s) |
37460529 |
| |
| Submission date |
Jan 01, 2023 |
| Last update date |
Jul 24, 2023 |
| Contact name |
Fengling Chen |
| E-mail(s) |
cfl15@tsinghua.org.cn
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| Organization name |
Tsinghua University
|
| Street address |
30 Shuangqing Rd.
|
| City |
Beijing |
| State/province |
Beijing |
| ZIP/Postal code |
100086 |
| Country |
China |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (40)
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| Relations |
| BioProject |
PRJNA917193 |
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