MOF-associated complexes ensure stem cell identity and Xist repression

Elife. 2014 May 19;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 and 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.DOI: http://dx.doi.org/10.7554/eLife.02024.001.

Keywords: D. melanogaster; X inactivation; acetylation; chromatin; epigenetics; transcription.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Chromatin / metabolism
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / metabolism
  • Histone Acetyltransferases / metabolism*
  • Mice
  • Protein Binding
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • X Chromosome Inactivation

Substances

  • Chromatin
  • RNA, Long Noncoding
  • XIST non-coding RNA
  • Histone Acetyltransferases
  • MOF protein, mouse

Grant support

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.