1. Genes and Chromosomes
  2. Genomics and Evolutionary Biology
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MOF-associated complexes ensure stem cell identity and Xist repression

  1. Tomasz Chelmicki
  2. Friederike Dündar
  3. Matthew Turley
  4. Tasneem Khanam
  5. Tugce Aktas
  6. Fidel Ramírez
  7. Anne-Valerie Gendrel
  8. Patrick R Wright
  9. Pavankumar Videm
  10. Rolf Backofen
  11. Edith Heard
  12. Thomas Manke
  13. Asifa Akhtar Is a corresponding author
  1. Max Planck Institute for Immunobiology and Epigenetics, Germany
  2. Institute Curie, France
  3. University of Freiburg, Germany
  4. Institut Curie, France
Research Article
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Cite as: eLife 2014;3:e02024 doi: 10.7554/eLife.02024

Abstract

Histone acetyl transferases (HATs) play distinct roles in many cellular processes and are frequently misregulated in cancers. Here, we study the regulatory potential of MYST1-(MOF)-containing MSL and NSL complexes in mouse embryonic stem cells (ESCs) and neuronal progenitors. We find that both complexes influence transcription by targeting promoters as well as TSS-distal enhancers. In contrast to flies, the MSL complex is not exclusively enriched on the X chromosome yet it is crucial for mammalian X chromosome regulation as it specifically regulates Tsix, the major repressor of Xist lncRNA. MSL depletion leads to decreased Tsix expression, reduced REX1 recruitment, and consequently, enhanced accumulation of Xist and variable numbers of inactivated X chromosomes during early differentiation. The NSL complex provides additional, Tsix-independent repression of Xist by maintaining pluripotency. MSL and NSL complexes therefore act synergistically by using distinct pathways to ensure a fail-safe mechanism for the repression of X inactivation in ESCs.

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Author details

  1. Tomasz Chelmicki

    1. Max Planck Institute for Immunobiology and Epigenetics, Freiburg, Germany
    Competing interests
    No competing interests declared.
  2. Friederike Dündar

    1. Max Planck Institute for Immunobiology and Epigenetics, Freiburg, Germany
    Competing interests
    No competing interests declared.
  3. Matthew Turley

    1. Max Planck Institute for Immunobiology and Epigenetics, Freiburg, Germany
    Competing interests
    No competing interests declared.
  4. Tasneem Khanam

    1. Max Planck Institute for Immunobiology and Epigenetics, Freiburg, Germany
    Competing interests
    No competing interests declared.
  5. Tugce Aktas

    1. Max Planck Institute for Immunobiology and Epigenetics, Freiburg, Germany
    Competing interests
    No competing interests declared.
  6. Fidel Ramírez

    1. Max Planck Institute for Immunobiology and Epigenetics, Freiburg, Germany
    Competing interests
    No competing interests declared.
  7. Anne-Valerie Gendrel

    1. Institute Curie, Paris, France
    Competing interests
    No competing interests declared.
  8. Patrick R Wright

    1. University of Freiburg, Freiburg, Germany
    Competing interests
    No competing interests declared.
  9. Pavankumar Videm

    1. University of Freiburg, Freiburg, Germany
    Competing interests
    No competing interests declared.
  10. Rolf Backofen

    1. University of Freiburg, Freiburg, Germany
    Competing interests
    No competing interests declared.
  11. Edith Heard

    1. Institut Curie, Paris, France
    Competing interests
    No competing interests declared.
  12. Thomas Manke

    1. Max Planck Institute for Immunobiology and Epigenetics, Freiburg, Germany
    Competing interests
    No competing interests declared.
  13. Asifa Akhtar

    1. Max Planck Institute for Immunobiology and Epigenetics, Freiburg, Germany
    For correspondence
    1. akhtar@immunbio.mpg.de
    Competing interests
    Asifa Akhtar, Reviewing editor, eLife.

Reviewing Editor

  1. Danny Reinberg, Reviewing Editor, Howard Hughes Medical Institute, New York University School of Medicine, United States

Publication history

  1. Received: December 6, 2013
  2. Accepted: May 11, 2014
  3. Accepted Manuscript published: May 19, 2014 (version 1)
  4. Version of Record published: June 17, 2014 (version 2)

Copyright

© 2014, Chelmicki et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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