ANP32E is a histone chaperone that removes H2A.Z from chromatin

Nature. 2014 Jan 30;505(7485):648-53. doi: 10.1038/nature12922. Epub 2014 Jan 22.


H2A.Z is an essential histone variant implicated in the regulation of key nuclear events. However, the metazoan chaperones responsible for H2A.Z deposition and its removal from chromatin remain unknown. Here we report the identification and characterization of the human protein ANP32E as a specific H2A.Z chaperone. We show that ANP32E is a member of the presumed H2A.Z histone-exchange complex p400/TIP60. ANP32E interacts with a short region of the docking domain of H2A.Z through a new motif termed H2A.Z interacting domain (ZID). The 1.48 Å resolution crystal structure of the complex formed between the ANP32E-ZID and the H2A.Z/H2B dimer and biochemical data support an underlying molecular mechanism for H2A.Z/H2B eviction from the nucleosome and its stabilization by ANP32E through a specific extension of the H2A.Z carboxy-terminal α-helix. Finally, analysis of H2A.Z localization in ANP32E(-/-) cells by chromatin immunoprecipitation followed by sequencing shows genome-wide enrichment, redistribution and accumulation of H2A.Z at specific chromatin control regions, in particular at enhancers and insulators.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cell Line
  • Cell Nucleus / chemistry
  • Cell Nucleus / metabolism
  • Chromatin / chemistry*
  • Chromatin / genetics
  • Chromatin / metabolism*
  • Chromatin Immunoprecipitation
  • Crystallography, X-Ray
  • DNA / genetics
  • DNA / metabolism
  • Genome, Human / genetics
  • Histones / chemistry
  • Histones / isolation & purification
  • Histones / metabolism*
  • Humans
  • Models, Molecular
  • Molecular Chaperones / chemistry
  • Molecular Chaperones / metabolism*
  • Molecular Sequence Data
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism*
  • Nucleosomes / chemistry
  • Nucleosomes / metabolism
  • Phosphoproteins / chemistry
  • Phosphoproteins / metabolism*
  • Protein Binding
  • Protein Conformation
  • Substrate Specificity


  • ANP32E protein, human
  • Chromatin
  • Histones
  • Molecular Chaperones
  • Nuclear Proteins
  • Nucleosomes
  • Phosphoproteins
  • DNA

Associated data

  • GEO/GSE51579
  • PDB/4CAY