Xist-dependent imprinted X inactivation and the early developmental consequences of its failure.
Nat Struct Mol Biol
; 24(3): 226-233, 2017 03.
Article
em En
| MEDLINE
| ID: mdl-28134930
ABSTRACT
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.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Impressão Genômica
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Desenvolvimento Embrionário
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Inativação do Cromossomo X
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RNA Longo não Codificante
Limite:
Animals
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article