| Summary: | <p>Abstract</p> <p>Background</p> <p>Expression of <it>Xist</it>, the master regulator of X chromosome inactivation, is extinguished in pluripotent cells, a process that has been linked to programmed X chromosome reactivation. The key pluripotency transcription factors Nanog, Oct4 and Sox2 are implicated in <it>Xist </it>gene extinction, at least in part through binding to an element located in <it>Xist </it>intron 1. Other pathways, notably repression by the antisense RNA <it>Tsix</it>, may also be involved.</p> <p>Results</p> <p>Here we employ a transgene strategy to test the role of the intron 1 element and <it>Tsix </it>in repressing <it>Xist </it>in ES cells. We find that deletion of the intron 1 element causes a small increase in <it>Xist </it>expression and that simultaneous deletion of the antisense regulator <it>Tsix </it>enhances this effect.</p> <p>Conclusion</p> <p>We conclude that <it>Tsix </it>and pluripotency factors act synergistically to repress <it>Xist </it>in undifferentiated embryonic stem cells. Double mutants do not exhibit maximal levels of <it>Xist </it>expression, indicating that other pathways also play a role.</p>
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