Xist-dependent imprinted X inactivation and the early developmental consequences of its failure

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Borensztein, Maud | Syx, Laurène | Ancelin, Katia | Diabangouaya, Patricia | Picard, Christel | Liu, Tao | Liang, Jun-Bin | Vassilev, Ivaylo | Galupa, Rafael | Servant, Nicolas | Barillot, Emmanuel | Surani, Azim | Chen, Chong-Jian | Heard, Edith

Edité par CCSD ; Nature Publishing Group -

International audience. 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.

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