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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 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.

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Figure 1: Immunopurification of e-H2A, e-H2A.Z and e-ANP32E predeposition complexes from soluble nuclear fractions.
Figure 2: The ANP32E ZID domain interacts with H2A.Z αC-helix.
Figure 3: Specific recognition of the H2A.Z/H2B pair by ANP32E.
Figure 4: Specific removal of H2A.Z from the nucleosome by ANP32E.
Figure 5: Genomic localization and chromatin enrichment of H2A.Z is dependent on ANP32E.

Accession codes


Gene Expression Omnibus

Protein Data Bank

Data deposits

ChIP-Seq datasets have been deposited in GEO under accession number GSE51579. X-ray crystallographic coordinates and structure factor files have been deposited in Protein Data Bank under accession number 4CAY.


  1. Iouzalen, N., Moreau, J. & Mechali, M. H2A.ZI, a new variant histone expressed during Xenopus early development exhibits several distinct features from the core histone H2A. Nucleic Acids Res. 24, 3947–3952 (1996)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Clarkson, M. J., Wells, J. R., Gibson, F., Saint, R. & Tremethick, D. J. Regions of variant histone His2AvD required for Drosophila development. Nature 399, 694–697 (1999)

    Article  ADS  CAS  PubMed  Google Scholar 

  3. Faast, R. et al. Histone variant H2A.Z is required for early mammalian development. Curr. Biol. 11, 1183–1187 (2001)

    Article  CAS  PubMed  Google Scholar 

  4. Billon, P. & Cote, J. Precise deposition of histone H2A.Z in chromatin for genome expression and maintenance. Biochim. Biophys. Acta 1819, 290–302 (2012)

    Article  CAS  Google Scholar 

  5. Mavrich, T. N. et al. A barrier nucleosome model for statistical positioning of nucleosomes throughout the yeast genome. Genome Res. 18, 1073–1083 (2008)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Raisner, R. M. et al. Histone variant H2A.Z marks the 5′ ends of both active and inactive genes in euchromatin. Cell 123, 233–248 (2005)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Zhang, H., Roberts, D. N. & Cairns, B. R. Genome-wide dynamics of Htz1, a histone H2A variant that poises repressed/basal promoters for activation through histone loss. Cell 123, 219–231 (2005)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Barski, A. et al. High-resolution profiling of histone methylations in the human genome. Cell 129, 823–837 (2007)

    Article  CAS  PubMed  Google Scholar 

  9. Zilberman, D., Coleman-Derr, D., Ballinger, T. & Henikoff, S. Histone H2A.Z and DNA methylation are mutually antagonistic chromatin marks. Nature 456, 125–129 (2008)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  10. Weber, C. M., Henikoff, J. G. & Henikoff, S. H2A.Z nucleosomes enriched over active genes are homotypic. Nature Struct. Mol. Biol. 17, 1500–1507 (2010)

    Article  CAS  Google Scholar 

  11. Conerly, M. L. et al. Changes in H2A.Z occupancy and DNA methylation during B-cell lymphomagenesis. Genome Res. 20, 1383–1390 (2010)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Guillemette, B. et al. Variant histone H2A.Z is globally localized to the promoters of inactive yeast genes and regulates nucleosome positioning. PLoS Biol. 3, e384 (2005)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Santisteban, M. S., Kalashnikova, T. & Smith, M. M. Histone H2A.Z regulates transcription and is partially redundant with nucleosome remodeling complexes. Cell 103, 411–422 (2000)

    Article  CAS  PubMed  Google Scholar 

  14. Kalocsay, M., Hiller, N. J. & Jentsch, S. Chromosome-wide Rad51 spreading and SUMO-H2A.Z-dependent chromosome fixation in response to a persistent DNA double-strand break. Mol. Cell 33, 335–343 (2009)

    Article  CAS  PubMed  Google Scholar 

  15. Rangasamy, D., Berven, L., Ridgway, P. & Tremethick, D. J. Pericentric heterochromatin becomes enriched with H2A.Z during early mammalian development. EMBO J. 22, 1599–1607 (2003)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Rangasamy, D., Greaves, I. & Tremethick, D. J. RNA interference demonstrates a novel role for H2A.Z in chromosome segregation. Nature Struct. Mol. Biol. 11, 650–655 (2004)

    Article  CAS  Google Scholar 

  17. Fan, J. Y., Gordon, F., Luger, K., Hansen, J. C. & Tremethick, D. J. The essential histone variant H2A.Z regulates the equilibrium between different chromatin conformational states. Nature Struct. Biol. 9, 172–176 (2002)

    Article  CAS  PubMed  Google Scholar 

  18. Meneghini, M. D., Wu, M. & Madhani, H. D. Conserved histone variant H2A.Z protects euchromatin from the ectopic spread of silent heterochromatin. Cell 112, 725–736 (2003)

    Article  CAS  PubMed  Google Scholar 

  19. Papamichos-Chronakis, M., Watanabe, S., Rando, O. J. & Peterson, C. L. Global regulation of H2A.Z localization by the INO80 chromatin-remodeling enzyme is essential for genome integrity. Cell 144, 200–213 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. van Attikum, H., Fritsch, O. & Gasser, S. M. Distinct roles for SWR1 and INO80 chromatin remodeling complexes at chromosomal double-strand breaks. EMBO J. 26, 4113–4125 (2007)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Hua, S. et al. Genomic analysis of estrogen cascade reveals histone variant H2A.Z associated with breast cancer progression. Mol. Syst. Biol. 4, 188 (2008)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Suto, R. K., Clarkson, M. J., Tremethick, D. J. & Luger, K. Crystal structure of a nucleosome core particle containing the variant histone H2A.Z. Nature Struct. Biol. 7, 1121–1124 (2000)

    Article  CAS  PubMed  Google Scholar 

  23. Hamiche, A. & Shuaib, M. Chaperoning the histone H3 family. Biochim. Biophys. Acta 1819, 230–237 (2012)

    Article  CAS  Google Scholar 

  24. Henikoff, S. & Ahmad, K. Assembly of variant histones into chromatin. Annu. Rev. Cell Dev. Biol. 21, 133–153 (2005)

    Article  CAS  PubMed  Google Scholar 

  25. Luk, E. et al. Chz1, a nuclear chaperone for histone H2AZ. Mol. Cell 25, 357–368 (2007)

    Article  CAS  PubMed  Google Scholar 

  26. Zhou, Z. et al. NMR structure of chaperone Chz1 complexed with histones H2A.Z-H2B. Nature Struct. Mol. Biol. 15, 868–869 (2008)

    Article  CAS  Google Scholar 

  27. Mizuguchi, G. et al. ATP-driven exchange of histone H2AZ variant catalyzed by SWR1 chromatin remodeling complex. Science 303, 343–348 (2003)

    Article  ADS  PubMed  CAS  Google Scholar 

  28. Kobor, M. S. et al. A protein complex containing the conserved Swi2/Snf2-related ATPase Swr1p deposits histone variant H2A.Z into euchromatin. PLoS Biol. 2, E131 (2004)

    Article  PubMed  PubMed Central  Google Scholar 

  29. Krogan, N. J. et al. A Snf2 family ATPase complex required for recruitment of the histone H2A variant Htz1. Mol. Cell 12, 1565–1576 (2003)

    Article  CAS  PubMed  Google Scholar 

  30. Cai, Y. et al. The mammalian YL1 protein is a shared subunit of the TRRAP/TIP60 histone acetyltransferase and SRCAP complexes. J. Biol. Chem. 280, 13665–13670 (2005)

    Article  CAS  PubMed  Google Scholar 

  31. Ikura, T. et al. Involvement of the TIP60 histone acetylase complex in DNA repair and apoptosis. Cell 102, 463–473 (2000)

    Article  CAS  PubMed  Google Scholar 

  32. Choi, J., Heo, K. & An, W. Cooperative action of TIP48 and TIP49 in H2A.Z exchange catalyzed by acetylation of nucleosomal H2A. Nucleic Acids Res. 37, 5993–6007 (2009)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Ruhl, D. D. et al. Purification of a human SRCAP complex that remodels chromatin by incorporating the histone variant H2A.Z into nucleosomes. Biochemistry 45, 5671–5677 (2006)

    Article  CAS  PubMed  Google Scholar 

  34. Nakatani, Y. & Ogryzko, V. Immunoaffinity purification of mammalian protein complexes. Methods Enzymol. 370, 430–444 (2003)

    Article  CAS  PubMed  Google Scholar 

  35. Drane, P., Ouararhni, K., Depaux, A., Shuaib, M. & Hamiche, A. The death-associated protein DAXX is a novel histone chaperone involved in the replication-independent deposition of H3.3. Genes Dev. 24, 1253–1265 (2010)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Doyon, Y., Selleck, W., Lane, W. S., Tan, S. & Cote, J. Structural and functional conservation of the NuA4 histone acetyltransferase complex from yeast to humans. Mol. Cell. Biol. 24, 1884–1896 (2004)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Matilla, A. & Radrizzani, M. The Anp32 family of proteins containing leucine-rich repeats. Cerebellum 4, 7–18 (2005)

    Article  CAS  PubMed  Google Scholar 

  38. Kular, R. K., Cvetanovic, M., Siferd, S., Kini, A. R. & Opal, P. Neuronal differentiation is regulated by leucine-rich acidic nuclear protein (LANP), a member of the inhibitor of histone acetyltransferase complex. J. Biol. Chem. 284, 7783–7792 (2009)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Jiang, X. et al. Distinctive roles of PHAP proteins and prothymosin-α in a death regulatory pathway. Science 299, 223–226 (2003)

    Article  ADS  CAS  PubMed  Google Scholar 

  40. Tochio, N. et al. Solution structure of histone chaperone ANP32B: interaction with core histones H3–H4 through its acidic concave domain. J. Mol. Biol. 401, 97–114 (2010)

    Article  CAS  PubMed  Google Scholar 

  41. Jensen, K., Santisteban, M. S., Urekar, C. & Smith, M. M. Histone H2A.Z acid patch residues required for deposition and function. Mol. Genet. Genom. 285, 287–296 (2011)

    Article  CAS  Google Scholar 

  42. Wu, W. H. et al. Swc2 is a widely conserved H2AZ-binding module essential for ATP-dependent histone exchange. Nature Struct. Mol. Biol. 12, 1064–1071 (2005)

    Article  CAS  Google Scholar 

  43. Luger, K., Mäder, A. W., Richmond, R. K., Sargent, D. F. & Richmond, T. J. Crystal structure of the nucleosome core particle at 2.8 A resolution. Nature 389, 251–260 (1997)

    Article  ADS  CAS  PubMed  Google Scholar 

  44. Hamiche, A. & Richard-Foy, H. Characterization of specific nucleosomal states by use of selective substitution reagents in model octamer and tetramer structures. Methods 19, 457–464 (1999)

    Article  CAS  PubMed  Google Scholar 

  45. Ku, M. et al. H2A.Z landscapes and dual modifications in pluripotent and multipotent stem cells underlie complex genome regulatory functions. Genome Biol. 13, R85 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Kelly, T. K. et al. H2A.Z maintenance during mitosis reveals nucleosome shifting on mitotically silenced genes. Mol. Cell 39, 901–911 (2010)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  47. Nekrasov, M. et al. Histone H2A.Z inheritance during the cell cycle and its impact on promoter organization and dynamics. Nature Struct. Mol. Biol. 19, 1076–1083 (2012)

    Article  CAS  Google Scholar 

  48. Shen, Y. et al. A map of the cis-regulatory sequences in the mouse genome. Nature 488, 116–120 (2012)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  49. Reilly, P. T. et al. Generation and characterization of the Anp32e-deficient mouse. PLoS ONE 5, e13597 (2010)

    Article  ADS  PubMed  PubMed Central  CAS  Google Scholar 

  50. Li, G., Levitus, M., Bustamante, C. & Widom, J. Rapid spontaneous accessibility of nucleosomal DNA. Nature Struct. Mol. Biol. 12, 46–53 (2005)

    Article  CAS  Google Scholar 

  51. Ouararhni, K. et al. The histone variant mH2A1.1 interferes with transcription by down-regulating PARP-1 enzymatic activity. Genes Dev. 20, 3324–3336 (2006)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Shuaib, M., Ouararhni, K., Dimitrov, S. & Hamiche, A. HJURP binds CENP-A via a highly conserved N-terminal domain and mediates its deposition at centromeres. Proc. Natl Acad. Sci. USA 107, 1349–1354 (2010)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  53. Luger, K., Rechsteiner, T. J. & Richmond, T. J. Expression and purification of recombinant histones and nucleosome reconstitution. Methods Mol. Biol. 119, 1–16 (1999)

    CAS  PubMed  Google Scholar 

  54. Hamiche, A., Kang, J. G., Dennis, C., Xiao, H. & Wu, C. Histone tails modulate nucleosome mobility and regulate ATP-dependent nucleosome sliding by NURF. Proc. Natl Acad. Sci. USA 98, 14316–14321 (2001)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  55. Simpson, R. T., Thoma, F. & Brubaker, J. M. Chromatin reconstituted from tandemly repeated cloned DNA fragments and core histones: a model system for study of higher order structure. Cell 42, 799–808 (1985)

    Article  CAS  PubMed  Google Scholar 

  56. Diebold, M. L., Fribourg, S., Koch, M., Metzger, T. & Romier, C. Deciphering correct strategies for multiprotein complex assembly by co-expression: application to complexes as large as the histone octamer. J. Struct. Biol. 175, 178–188 (2011)

    Article  CAS  PubMed  Google Scholar 

  57. Otwinowski, Z. & Minor, W. Processing of X-ray diffraction data collected in oscillation mode. Methods Enzymol. 276, 307–326 (1997)

    Article  CAS  PubMed  Google Scholar 

  58. Vagin, A. & Teplyakov, A. Molecular replacement with MOLREP. Acta Crystallogr. D 66, 22–25 (2010)

    Article  CAS  PubMed  Google Scholar 

  59. Adams, P. D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D 66, 213–221 (2010)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Blanc, E. et al. Refinement of severely incomplete structures with maximum likelihood in BUSTER-TNT. Acta Crystallogr. D 60, 2210–2221 (2004)

    Article  CAS  PubMed  Google Scholar 

  61. Emsley, P. & Cowtan, K. Coot: model-building tools for molecular graphics. Acta Crystallogr. D 60, 2126–2132 (2004)

    Article  PubMed  CAS  Google Scholar 

  62. Bond, C. S. & Schuttelkopf, A. W. ALINE: a WYSIWYG protein-sequence alignment editor for publication-quality alignments. Acta Crystallogr. D 65, 510–512 (2009)

    Article  CAS  PubMed  Google Scholar 

  63. Langmead, B., Trapnell, C., Pop, M. & Salzberg, S. L. Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol. 10, R25 (2009)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. Zhang, Y. et al. Model-based analysis of ChIP-Seq (MACS). Genome Biol. 9, R137 (2008)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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We thank I. Davidson, P. Antony, J. Cavarelli and D. Moras for reading the manuscript, and V. Cura and A. McEwen for help during data collection. This work was supported by CNRS, INSERM, Université de Strasbourg, and by grants from INCa (INCa_4496 and INCa_4454), ANR (VariZome, ANR-12-BSV8-0018-01; Nucleoplat, NT09_476241), the Association pour la Recherche sur le Cancer, La Fondation pour la Recherche Médicale, La Ligue Nationale contre le Cancer (Equipe labellisée, to A.H. and S.D.), the French Infrastructure for Integrated Structural Biology (FRISBI; ANR-10-INSB-05-01) and by Instruct (ESFRI). A.O. acknowledges the Association pour la Recherche sur le Cancer for Financial support. K.P. was supported by la Ligue Nationale contre le Cancer.

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Authors and Affiliations



A.H. conceived and supervised the project. A.O. and K.O. built constructs and performed complex purifications and chromatin assembly/eviction assays. C.R., M.L.D. and M.M. solved the ANP32E-ZID–H2A.Z/H2B structure. C.P. and K.P. performed ChIP-seq experiments. P.T.R. and T.W.M. provided the ANP32E−/− mice. I.S. and K.O. generated the ANP32E−/− MEF cells. C.P. and L.R. conducted all bioinformatics analyses. A.H., C.R. and S.D. designed experiments, analysed data and wrote the paper.

Corresponding authors

Correspondence to Stefan Dimitrov, Christophe Romier or Ali Hamiche.

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The authors declare no competing financial interests.

Extended data figures and tables

Extended Data Figure 1 ANP32E and are stably associated in an H2A.Z subcomplex.

a, Control (Ctrl) and e-H2A- and e-H2A.Z-expressing cells were stained with anti-HA (green) and DAPI (blue) (upper panel). Extracts from control and e-H2A.Z-expressing HeLa cells were blotted with a monoclonal anti-H2A.Z antibody (lower panel). b, Silver staining of e-H2A.Z predeposition complex fractionated on a glycerol gradient (upper panel). Fractions were pooled as indicated at the top of the gel (low molecular mass complexes, medium molecular mass complexes and high molecular mass complexes) and analysed by mass spectrometry. Lower panel, immunoblotting of fractions containing e-H2A.Z nuclear subcomplexes with the indicated antibodies. c, Mass spectrometry analyses of the different H2A.Z subcomplexes. d, GST pull-down assays show that ANP32E directly interacts through its N-terminal domain with MRGBP.

Extended Data Figure 2 Mapping of the ANP32E and H2A.Z interaction domains.

a, b, GST pull-down assays using ANP32E deletion mutants. Upper panels, the acidic very C-terminal conserved domain of ANP32E is required for the interaction with H2A.Z/H2B. Lower panels, immunoblotting using anti-Flag antibody of Flag-tagged H2A.Z. c, Deletion analysis of the ANP32E very C-terminal conserved domain. The 215–240 amino-acid region is the minimal domain required for interaction with H2A.Z/H2B. d, Same as in a and b, using H2A.Z C-terminal deletion mutants. Deletion of a region encompassing the H2A.Z M6 cassette impairs binding to ANP32E.

Extended Data Figure 3 ANP32E-ZID is highly conserved.

a, Multiple alignment of ANP32E from various organisms, indicating that ANP32E is a vertebrate-specific H2A.Z histone chaperone. The ANP32E-ZID defines the minimal H2A.Z/H2B interacting domain and corresponds to the primary conserved C-terminal region of ANP32E. b, Multiple alignment of the human ANP32 protein family showing the presence of a specific insertion in ANP32E embedded in its ZID domain. The numbering above the sequences corresponds to human ANP32E. Sequence conservation is shown by shading, from red (high) to green/blue (low).

Extended Data Figure 4 H2A.Z αC-helix undergoes a large conformational change upon ANP32E-ZID binding.

ac, The conformation of the α3–αC region of H2A.Z is shown in the H2A.Z nucleosome (a), the ANP32E-ZID–H2A.Z/H2B complex (b) and as a superposition of views from panels a and b (c), with the ANP32E-ZID αN-helix hidden (upper panels) or shown (lower panels). These views highlight the extension of the H2A.Z αC-helix occurring upon ANP32E-ZID binding and show that the ANP32E-ZID αN-helix occupies a position previously filled by the H2A.Z docking domain.

Extended Data Figure 5 Stereo views of the interactions made by ANP32E-ZID and the H2A.Z/H2B pair.

a, Close-up view of the interaction between ANP32E-ZID (blue) αN, H2A.Z (red) α3–αC and H2B (light grey) α2 helices. b, Close-up view of the interaction between ANP32E-ZID and the H2A.Z/H2B region involved in DNA interaction close to the entry/exit points of the nucleosome. c, Alignment of the ANP32E-ZID showing the conservation of the residues (yellow triangles) that interact with the H2A.Z/H2B pair.

Extended Data Figure 6 Mutational analysis of ANP32E-H2A.Z interaction.

a, GST pull-down experiments and anti-Flag immunoblotting showing that a single glycine insertion at position 101 of H2A.Z (H2A.Z-G101) prevents its interaction with ANP32E. b, Multiple alignment of human canonical and variant H2A histones showing the presence of an extra residue (generally a glycine) in their M6 cassette compared with H2A.Z (yellow diamond). c, Co-expression in bacteria of full-length ANP32E, either wild type or mutant, with the H2A.Z/H2B pair. *Proteolytic fragments of ANP32E. d, Purification (left panel) and western blotting (right panel) of the in vivo complexes incorporating ANP32E either wild type or mutated on the residues highlighted in panel e. e, Schematic view of human ANP32E-ZID showing the residues (yellow triangles) that interact with the H2A.Z/H2B pair and that are mutated in the m1m2 mutant.

Extended Data Figure 7 Specific removal of H2A.Z from the nucleosome by ANP32E.

a, Effects of increasing amounts of competitor supercoiled plasmid DNA on ANP32E-mediated H2A.Z eviction from nucleosomes reconstituted on the negatively supercoiled human α-satellite 360 bp DNA minicircle corresponding to topoisomer −1. The reaction products were analysed on native PAGE. b, c, Effects of increasing amounts of ANP32E (b) or NAP1 (c) on H2A.Z/H2B or H2A/H2B dimer deposition on (H3/H4)2 tetrasome particles reconstituted on topoisomer −1. d, Mononucleosome assembly to generate H2A or H2A.Z mononucleosomes by salt-jump dialysis. e, Effects of increasing amounts of e-ANP32E complex ( on H2A.Z incorporation on bead-immobilized H2A nucleosomes. is not able to catalyse replacement of H2A with H2A.Z in vitro.

Extended Data Figure 8 Genome-wide distribution of H2A.Z in ANP32E WT and knockout MEF cells.

a, Heat-map view of genome-wide H2A.Z binding sites in wild-type and knockout cells at promoter-proximal sites (left panel) and distal sites (right panel). b, Heat-maps of H2A.Z-occupied and H2A.Z-free TSS in MEF cells from wild-type and ANP32E knockout MEFs (left-most panels). Sub-clusters in H2A.Z-occupied TSS (middle panel) were generated to highlight different distribution patterns of H2A.Z (percentage fractions are indicated) in ANP32E wild-type (blue) and knockout (red) MEFs (right panels). c, H2A.Z preferentially binds CpG-containing promoters.

Extended Data Figure 9 Steric hindrances that cause H2A.Z/H2B eviction from the nucleosome upon ANP32E binding.

a, Superposition (middle panel) of the ANP32E-ZID–H2A.Z/H2B complex (left panel) onto the H2A.Z/H2B pair in a nucleosomal context (right panel). Several steric hindrances (indicated by arrows) are observed at the DNA level as well as at the interface with the nucleosomal H3/H4 pair (coloured green and pink, respectively) that are incompatible with stable H2A.Z/H2B binding to the nucleosome.

Extended Data Table 1 Mass spectrometry analysis of the e-H2A, e-H2A.Z, e-ANP32E and e-H2A.ZNKLLG complexes

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Obri, A., Ouararhni, K., Papin, C. et al. ANP32E is a histone chaperone that removes H2A.Z from chromatin. Nature 505, 648–653 (2014).

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