pluripotency factor binding and tsix expression act synergistically to repress xist in undifferentiated embryonic stem cells多能性因子绑定和tsix表达式协同作用抑制xist未分化的胚胎干细胞.pdfVIP

Nesterova et al. Epigenetics Chromatin 2011, 4:17 /content/4/1/17 RESEARCH Open Access Pluripotency factor binding and Tsix expression act synergistically to repress Xist in undifferentiated embryonic stem cells 1† 1,2† 1,3 1 1 Tatyana B Nesterova , Claire E Senner , Janina Schneider , Tilly Alcayna-Stevens , Anna Tattermusch , Myriam Hemberger2 and Neil Brockdorff1* 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. Background which are derived from the ICM, mirror this ground In female mammals a developmentally regulated process, state, retaining two active X chromosomes [6,7]. In con- X inactivation, ensures silencing of a single X chromo-