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Molecular Coupling of Xist Regulation and Pluripotency

Pluripotency key factors bind to Xist intron 1 in undifferentiated embryonic stem cells, report research groups from the Pasteur Institute in Paris and the University of Edinburgh, UK. During murine embryogenesis, the imprinted X chromosome inactivation can be reprogrammed in the inner cell mass of a pluripotent female blastocyst. The reversion is triggered by repression of Xist from the paternal X chromosome. The three main genetic factors underlying pluripotency, , /4 and , bind to Xist intron 1.

In -/- embryonic stem cells, a slight up-regulation of Xist is observed if /4 and binding is normal. The up-regulation is reversible. Release of all three factors from Xist intron 1 results in a rapid ectopic accumulation of Xist RNA.
The three main factors for pluripotency seem to cooperate and repress Xist. X chromosome inactivation reversal is therefore linked to the control of pluripotency during murine embryogenesis.

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