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Pluripotency factor binding and Tsix expression act synergistically to repress Xist in undifferentiated embryonic stem cells

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Author(s): Nesterova Tatyana B | Senner Claire E | Schneider Janina | Alcayna-Stevens Tilly | Tattermusch Anna | Hemberger Myriam | Brockdorff Neil

Journal: Epigenetics & Chromatin
ISSN 1756-8935

Volume: 4;
Issue: 1;
Start page: 17;
Date: 2011;
Original page

ABSTRACT
Abstract Background Expression of Xist, 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 Xist gene extinction, at least in part through binding to an element located in Xist intron 1. Other pathways, notably repression by the antisense RNA Tsix, may also be involved. Results Here we employ a transgene strategy to test the role of the intron 1 element and Tsix in repressing Xist in ES cells. We find that deletion of the intron 1 element causes a small increase in Xist expression and that simultaneous deletion of the antisense regulator Tsix enhances this effect. Conclusion We conclude that Tsix and pluripotency factors act synergistically to repress Xist in undifferentiated embryonic stem cells. Double mutants do not exhibit maximal levels of Xist expression, indicating that other pathways also play a role.

Tango Jona
Tangokurs Rapperswil-Jona

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