| First Author | Borensztein M | Year | 2017 |
| Journal | Nat Struct Mol Biol | Volume | 24 |
| Issue | 3 | Pages | 226-233 |
| PubMed ID | 28134930 | Mgi Jnum | J:320748 |
| Mgi Id | MGI:6875440 | Doi | 10.1038/nsmb.3365 |
| Citation | Borensztein M, et al. (2017) Xist-dependent imprinted X inactivation and the early developmental consequences of its failure. Nat Struct Mol Biol 24(3):226-233 |
| abstractText | The long noncoding RNA Xist is expressed from only the paternal X chromosome in mouse preimplantation female embryos and mediates transcriptional silencing of that chromosome. In females, absence of Xist leads to postimplantation lethality. Here, through single-cell RNA sequencing of early preimplantation mouse embryos, we found that the initiation of imprinted X-chromosome inactivation absolutely requires Xist. Lack of paternal Xist leads to genome-wide transcriptional misregulation in the early blastocyst and to failure to activate the extraembryonic pathway that is essential for postimplantation development. We also demonstrate that the expression dynamics of X-linked genes depends on the strain and parent of origin as well as on the location along the X chromosome, particularly at the first 'entry' sites of Xist. This study demonstrates that dosage-compensation failure has an effect as early as the blastocyst stage and reveals genetic and epigenetic contributions to orchestrating transcriptional silencing of the X chromosome during early embryogenesis. |
