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

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 [alpha]-helix. Finally, analysis of H2A.Z localization in ANP32E.sup.-/- 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. Human protein ANP32E is a histone chaperone that promotes removal of H2A.Z from chromatin. Chaperoning a histone variant The histone H2A.Z is a variant of histone H2A, one of the canonical histones present in the chromatin of eukaryotic cells. H2A.Z has important functions in transcription and other nuclear processes. Here, Ali Hamiche and colleagues identify the human protein ANP32E as an H2A.Z chaperone capable of promoting the removal of H2A.Z from chromatin. Biochemical and structural data indicate the molecular basis for H2A.Z recognition and eviction by ANP32E, and genome-wide mapping analyses reveal how ANP32E regulates H2A.Z occupancy at important regulatory regions of the genome.
Author(s): Arnaud Obri [sup.1] , Khalid Ouararhni [sup.1] , Christophe Papin [sup.1] , Marie-Laure Diebold [sup.2] , Kiran Padmanabhan [sup.3] , Martin Marek [sup.2] , Isabelle Stoll [sup.1] , Ludovic [...]