title: Pluripotency factor binding and Tsix expression act synergistically to repress Xist in undifferentiated embryonic stem cells.
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.
  
  
  CONCLUSIONS
  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.
authors: Developmental Epigenetics Group, Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK.
authors: Tatyana B
authors: TB
authors: Nesterova
authors: Developmental Epigenetics Group, Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK.|Epigenetics Programme, The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
authors: Claire E
authors: CE
authors: Senner
authors: Developmental Epigenetics Group, Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK.|Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford University, Oxford, OX3 9DS, UK.
authors: Janina
authors: J
authors: Schneider
authors: Developmental Epigenetics Group, Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK.
authors: Tilly
authors: T
authors: Alcayna-Stevens
authors: Developmental Epigenetics Group, Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK.
authors: Anna
authors: A
authors: Tattermusch
authors: Epigenetics Programme, The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
authors: Myriam
authors: M
authors: Hemberger
authors: Developmental Epigenetics Group, Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK.
authors: Neil
authors: N
authors: Brockdorff