| First Author | Nie X | Year | 2023 |
| Journal | Nat Commun | Volume | 14 |
| Issue | 1 | Pages | 4275 |
| PubMed ID | 37460529 | Mgi Jnum | J:338266 |
| Mgi Id | MGI:7510619 | Doi | 10.1038/s41467-023-39924-1 |
| Citation | Nie X, et al. (2023) Maternal TDP-43 interacts with RNA Pol II and regulates zygotic genome activation. Nat Commun 14(1):4275 |
| abstractText | 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 the two-cell stage. 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. |
