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Updated: May 28, 2026

A Simple Method to Identify Kinases That Regulate Embryonic Stem Cell Pluripotency by High-throughput Inhibitor Screening
07:18

A Simple Method to Identify Kinases That Regulate Embryonic Stem Cell Pluripotency by High-throughput Inhibitor Screening

Published on: May 12, 2017

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

Tatyana B Nesterova1, Claire E Senner1,2, Janina Schneider1,3

  • 1Developmental Epigenetics Group, Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK.

Epigenetics & Chromatin
|October 11, 2011
PubMed
Abstract

Insights

Tsix and pluripotency factors work together to silence Xist in embryonic stem cells. This repression is crucial for maintaining pluripotency and X chromosome regulation.

Area of Science:

  • Epigenetics and Gene Regulation
  • Developmental Biology
  • Stem Cell Biology

Background:

  • Xist is essential for X chromosome inactivation, but its expression is silenced in pluripotent cells.
  • Pluripotency transcription factors (Nanog, Oct4, Sox2) and Tsix RNA are implicated in Xist gene silencing.
  • An element in Xist intron 1 is a potential binding site for factors involved in Xist repression.

Purpose of the Study:

  • To investigate the roles of the Xist intron 1 element and Tsix in repressing Xist expression in embryonic stem (ES) cells.
  • To determine if pluripotency factors and Tsix act synergistically to regulate Xist.
  • To identify other potential pathways involved in Xist repression.

Main Methods:

  • Utilized a transgene strategy in ES cells to study Xist regulation.
  • Generated cell lines with deletions of the Xist intron 1 element and/or Tsix.
  • Quantified Xist expression levels in engineered ES cell lines.

Main Results:

  • Deletion of the Xist intron 1 element led to a modest increase in Xist expression.
  • Simultaneous deletion of both the intron 1 element and Tsix resulted in a more significant enhancement of Xist expression.
  • Maximal Xist expression levels were not achieved even in double mutants, suggesting additional regulatory mechanisms.

Conclusions:

  • Tsix and pluripotency factors cooperatively repress Xist expression in undifferentiated ES cells.
  • These findings highlight a synergistic mechanism for Xist silencing essential for maintaining pluripotency.
  • Other regulatory pathways contribute to the complete repression of Xist in ES cells.

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