The Discovery And Biochemical Studies Of The Specific Molecular Chaperone Anp32e Of Histone H2A.Z In Higher Animals

Histone variants demarcate distinct chromatin regions to specify dedicated functions. Histone H2A.Z is a well-studied H2A variant that is enriched around the transcription start sites (TSS). Swrl complex and its mammalian counterpart the SRCAP complex are main proteins depositing H2A.Z. In addition, Chzl is an H2A.Z-sepcific chaperone in fungi. Here we report a higher eukaryotes specific H2A.Z-specific chaperone Anp32e. Using biochemical purification, we purified Anp32e as an H2A.Z-specific chaperone. Anp32e specifically associates with H2A.Z-H2B dimers, but not with H2A-H2B dimers in vivo. In addition, Anp32e selectively associates with H2A.Z-H2B dimers, but not with H2A.Z containing nucleosomes. Anp32e selectively interacts with the C-terminal region of H2A.Z, which differs from canonical histone H2A. Like histone chaperone Napl, Anp32e is capable of dissociating non-nucleosomal aggregates formed by DNA and H2A-H2B dimers, with a preference towards H2A.Z-H2B dimers. Finally, genome-wide profiling of Anp32e revealed remarkable co-occupancy between Anp32e and H2A.Z in mammalian cells, suggesting a role of Anp32e in regulating H2A.Z deposition.