Anp32e, a higher eukaryotic histone chaperone directs preferential recognition for H2A,Z

H2A.Z is a highly conserved histone variant in all species. The chromatin deposition of H2A.Z is specifically cata- lyzed by the yeast chromatin remodeling complex SWR1 and its mammalian counterpart SRCAP. However, the mechanism by which H2A.Z is preferentially recognized by non-histone proteins remains elusive. Here we identified Anp32e, a novel higher eukaryote-specific histone chaperone for H2A.Z. Anp32e preferentially associates with H2A. Z-H2B dimers rather than H2A-H2B dimers in vitro and in vivo and dissociates non-nucleosomal aggregates formed by DNA and H2A-H2B. We determined the crystal structure of the Anp32e chaperone domain （186-232） in complex with the H2A.Z-H2B dimer. In this structure, the region containing Anp32e residues 214-224, which is absent in other Anp32 family proteins, specifically interacts with the extended H2A.Z aC helix, which exhibits an unexpected confor- mational change. Genome-wide profiling of Anp32e revealed a remarkable co-occupancy between Anp32e and H2A. Z. Cells overexpressing Anp32e displayed a strong global H2A.Z loss at the ＋1 nucleosomes, whereas cells depleted of Anp32e displayed a moderate global H2A.Z increase at the ＋1 nucleosomes. This suggests that Anp32e may help to resolve the non-nucleosomal H2A.Z aggregates and also facilitate the removal of H2A.Z at the ＋1 nucleosomes, and the latter may help RNA polymerase II to pass the first nucleosomal barrier.