title: Anp32e, a higher eukaryotic histone chaperone directs preferential recognition for H2A.Z.
abstract: H2A.Z is a highly conserved histone variant in all species. The chromatin deposition of H2A.Z is specifically catalyzed 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 αC helix, which exhibits an unexpected conformational 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.
authors.affiliation: 1] Graduate Program, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China [2] National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Mao
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Pan
authors.affiliation: College of Plant Science and Technology, Beijing University of Agriculture, Beijing 102206, China.
authors.forename: Weixiang
authors.initials: W
authors.lastname: Wang
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Shan
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Dong
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Liang
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Linchang
authors.initials: L
authors.lastname: Dai
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Ding
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: She
authors.initials: S
authors.lastname: Chen
authors.affiliation: 1] National Institute of Biological Sciences, Beijing 102206, China [2] National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Zhuqiang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: 1] Graduate Program, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China [2] National Institute of Biological Sciences, Beijing 102206, China [3] National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Zhu
authors.affiliation: 1] National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China [2] Center for Age-related Diseases, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhou
mesh_terms: D000595:Amino Acid Sequence; D005057:Eukaryotic Cells / Q000378:metabolism*; D006367:HeLa Cells; D006657:Histones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000737:chemistry / Q000502:physiology*; D062105:Molecular Docking Simulation; D009687:Nuclear Proteins / Q000737:chemistry / Q000502:physiology*; D009707:Nucleosomes / Q000378:metabolism; D010750:Phosphoproteins / Q000737:chemistry / Q000502:physiology*; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
chemical_list: C490336:ANP32E protein, human; D006657:Histones; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D009707:Nucleosomes; D010750:Phosphoproteins; C077020:histone H2A.F-Z