Foxa2 and H2A.Z mediate nucleosome depletion during embryonic stem cell differentiation

Cell. 2012 Dec 21;151(7):1608-16. doi: 10.1016/j.cell.2012.11.018.


Nucleosome occupancy is fundamental for establishing chromatin architecture. However, little is known about the relationship between nucleosome dynamics and initial cell lineage specification. Here, we determine the mechanisms that control global nucleosome dynamics during embryonic stem (ES) cell differentiation into endoderm. Both nucleosome depletion and de novo occupation occur during the differentiation process, with higher overall nucleosome density after differentiation. The variant histone H2A.Z and the winged helix transcription factor Foxa2 both act to regulate nucleosome depletion and gene activation, thus promoting ES cell differentiation, whereas DNA methylation promotes nucleosome occupation and suppresses gene expression. Nucleosome depletion during ES cell differentiation is dependent on Nap1l1-coupled SWI/SNF and INO80 chromatin remodeling complexes. Thus, both epigenetic and genetic regulators cooperate to control nucleosome dynamics during ES cell fate decisions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation*
  • Chromatin Assembly and Disassembly*
  • Chromatin Immunoprecipitation
  • DNA Methylation
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / metabolism*
  • Hepatocyte Nuclear Factor 3-beta / metabolism*
  • Histones / genetics
  • Histones / metabolism*
  • Mice
  • Nucleosomes / metabolism*


  • Foxa2 protein, mouse
  • Histones
  • Nucleosomes
  • histone H2A.F-Z
  • Hepatocyte Nuclear Factor 3-beta