Within the nucleus, the interplay between lineage-specific transcription factors and chromatin dynamics defines cellular identity. Control of this interplay is necessary to properly balance stability and plasticity during the development and entire life span of multicellular organisms. Here, we present our current knowledge of the contribution of histone H3 variants to chromatin dynamics during development. We review the network of histone chaperones that governs their deposition timing and sites of incorporation and highlight how their distinct distribution impacts genome organization and function. We integrate the importance of H3 variants in the context of nuclear reprogramming and cell differentiation, and, using the centromere as a paradigm, we describe a case in which the identity of a given genomic locus is propagated across different cell types. Finally, we compare development to changes in stress and disease. Both physiological and pathological settings underline the importance of H3 dynamics for genome and chromatin integrity.


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Literature Cited

  1. Adam S, Polo SE, Almouzni G. 2013. Transcription recovery after DNA damage requires chromatin priming by the H3.3 histone chaperone HIRA. Cell 155:194–106 [Google Scholar]
  2. Ai X, Parthun MR. 2004. The nuclear Hat1p/Hat2p complex: a molecular link between type B histone acetyltransferases and chromatin assembly. Mol. Cell 14:2195–205 [Google Scholar]
  3. Aida M, Hamad N, Stanlie A, Begum NA, Honjo T. 2013. Accumulation of the FACT complex, as well as histone H3.3, serves as a target marker for somatic hypermutation. Proc. Natl. Acad. Sci. USA 110:197784–89 [Google Scholar]
  4. Aihara K, Mukasa A, Gotoh K, Saito K, Nagae G. et al. 2014. H3F3A K27M mutations in thalamic gliomas from young adult patients. Neuro-Oncol. 16:1140–46 [Google Scholar]
  5. Akiyama T, Suzuki O, Matsuda J, Aoki F. 2011. Dynamic replacement of histone H3 variants reprograms epigenetic marks in early mouse embryos. PLOS Genet. 7:10e1002279 [Google Scholar]
  6. Albig W, Ebentheuer J, Klobeck G, Kunz J, Doenecke D. 1996. A solitary human H3 histone gene on chromosome 1. Hum. Genet. 97:4486–91 [Google Scholar]
  7. Allan RS, Zueva E, Cammas F, Schreiber HA, Masson V. et al. 2012. An epigenetic silencing pathway controlling T helper 2 cell lineage commitment. Nature 487:7406249–53 [Google Scholar]
  8. Amato A, Schillaci T, Lentini L, Di Leonardo A. 2009. CENPA overexpression promotes genome instability in pRb-depleted human cells. Mol. Cancer 8:1119 [Google Scholar]
  9. Ambartsumyan G, Gill RK, Perez SD, Conway D, Vincent J. et al. 2010. Centromere protein A dynamics in human pluripotent stem cell self-renewal, differentiation and DNA damage. Hum. Mol. Genet. 19:203970–82 [Google Scholar]
  10. Andrews AJ, Luger K. 2011. Nucleosome structure(s) and stability: variations on a theme. Annu. Rev. Biophys. 40:99–117 [Google Scholar]
  11. Ask K, Jasencakova Z, Menard P, Feng Y, Almouzni G, Groth A. 2012. Codanin-1, mutated in the anaemic disease CDAI, regulates Asf1 function in S-phase histone supply. EMBO J. 31:82013–23 [Google Scholar]
  12. Banaszynski LA, Wen D, Dewell S, Whitcomb SJ, Lin M. et al. 2013. Hira-dependent histone H3.3 deposition facilitates PRC2 recruitment at developmental loci in ES cells. Cell 155:1107–20 [Google Scholar]
  13. Banumathy G, Somaiah N, Zhang R, Tang Y, Hoffmann J. et al. 2009. Human UBN1 is an ortholog of yeast Hpc2p and has an essential role in the HIRA/ASF1a chromatin-remodeling pathway in senescent cells. Mol. Cell. Biol. 29:3758–70 [Google Scholar]
  14. Barnhart MC, Kuich PHJL, Stellfox ME, Ward JA, Bassett EA. et al. 2011. HJURP is a CENP-A chromatin assembly factor sufficient to form a functional de novo kinetochore. J. Cell Biol. 194:2229–43 [Google Scholar]
  15. Behjati S, Tarpey PS, Presneau N, Scheipl S, Pillay N. et al. 2013. Distinct H3F3A and H3F3B driver mutations define chondroblastoma and giant cell tumor of bone. Nat. Genet. 45:121479–82 [Google Scholar]
  16. Belotserkovskaya R, Oh S, Bondarenko VA, Orphanides G, Studitsky VM, Reinberg D. 2003. FACT facilitates transcription-dependent nucleosome alteration. Science 301:56361090–93 [Google Scholar]
  17. Bender S, Tang Y, Lindroth AM, Hovestadt V, Jones DTW. et al. 2013. Reduced H3K27me3 and DNA hypomethylation are major drivers of gene expression in K27M mutant pediatric high-grade gliomas. Cancer Cell 24:5660–72 [Google Scholar]
  18. Bérubé NG, Mangelsdorf M, Jagla M, Vanderluit J, Garrick D. et al. 2005. The chromatin-remodeling protein ATRX is critical for neuronal survival during corticogenesis. J. Clin. Investig. 115:2258–67 [Google Scholar]
  19. Bjerke L, Mackay A, Nandhabalan M, Burford A, Jury A. et al. 2013. Histone H3.3 mutations drive pediatric glioblastoma through upregulation of MYCN. Cancer Discov. 3:512–19 [Google Scholar]
  20. Black BE, Bassett EA. 2008. The histone variant CENP-A and centromere specification. Curr. Opin. Cell Biol. 20:191–100 [Google Scholar]
  21. Bonnefoy E, Orsi GA, Couble P, Loppin B. 2007. The essential role of Drosophila HIRA for de novo assembly of paternal chromatin at fertilization. PLOS Genet. 3:101991–2006 [Google Scholar]
  22. Bortvin A, Winston F. 1996. Evidence that Spt6p controls chromatin structure by a direct interaction with histones. Science 272:52671473–76 [Google Scholar]
  23. Briggs R, King TJ. 1952. Transplantation of living nuclei from blastula cells into enucleated frogs’ eggs. Proc. Natl. Acad. Sci. USA 38:5455–63 [Google Scholar]
  24. Brykczynska U, Hisano M, Erkek S, Ramos L, Oakeley EJ. et al. 2010. Repressive and active histone methylation mark distinct promoters in human and mouse spermatozoa. Nat. Struct. Mol. Biol. 17:6679–87 [Google Scholar]
  25. Buczkowicz P, Hoeman C, Rakopoulos P, Pajovic S, Letourneau L. et al. 2014. Genomic analysis of diffuse intrinsic pontine gliomas identifies three molecular subgroups and recurrent activating ACVR1 mutations. Nat. Genet. 46:5451–56 [Google Scholar]
  26. Burgess RJ, Zhang Z. 2013. Histone chaperones in nucleosome assembly and human disease. Nat. Struct. Mol. Biol. 20:114–22 [Google Scholar]
  27. Burrack LS, Berman J. 2012. Neocentromeres and epigenetically inherited features of centromeres. Chromosome Res. 20:5607–19 [Google Scholar]
  28. Bush KM, Yuen BT, Barrilleaux BL, Riggs JW, O'Geen H. et al. 2013. Endogenous mammalian histone H3.3 exhibits chromatin-related functions during development. Epigenet. Chromatin 6:17 [Google Scholar]
  29. Campos EI, Fillingham J, Li G, Zheng H, Voigt P. et al. 2010. The program for processing newly synthesized histones H3.1 and H4. Nat. Struct. Mol. Biol. 17:111343–51 [Google Scholar]
  30. Casanova M, Pasternak M, El Marjou F, Le Baccon P, Probst AV, Almouzni G. 2013. Heterochromatin reorganization during early mouse development requires a single-stranded noncoding transcript. Cell Rep. 4:61156–67 [Google Scholar]
  31. Chen C-C, Dechassa ML, Bettini E, Ledoux MB, Belisario C. et al. 2014. CAL1 is the Drosophila CENP-A assembly factor. J. Cell Biol. 204:3313–29 [Google Scholar]
  32. Chen P, Zhao J, Wang Y, Wang M, Long H. et al. 2013. H3.3 actively marks enhancers and primes gene transcription via opening higher-ordered chromatin. Genes Dev. 27:192109–24 [Google Scholar]
  33. Conn KL, Hendzel MJ, Schang LM. 2013. The differential mobilization of histones H3.1 and H3.3 by herpes simplex virus 1 relates histone dynamics to the assembly of viral chromatin. PLOS Pathog. 9:10e1003695 [Google Scholar]
  34. Cook AJL, Gurard-Levin ZA, Vassias I, Almouzni G. 2011. A specific function for the histone chaperone NASP to fine-tune a reservoir of soluble H3-H4 in the histone supply chain. Mol. Cell 44:6918–27 [Google Scholar]
  35. Corpet A, De Koning L, Toedling J, Savignoni A, Berger F. et al. 2010. Asf1b, the necessary Asf1 isoform for proliferation, is predictive of outcome in breast cancer. EMBO J. 30:3480–93 [Google Scholar]
  36. Couldrey C, Carlton MB, Nolan PM, Colledge WH, Evans MJ. 1999. A retroviral gene trap insertion into the histone 3.3A gene causes partial neonatal lethality, stunted growth, neuromuscular deficits and male sub-fertility in transgenic mice. Hum. Mol. Genet. 8:132489–95 [Google Scholar]
  37. Cox SG, Kim H, Garnett AT, Medeiros DM, An W, Crump JG. 2012. An essential role of variant histone H3.3 for ectomesenchyme potential of the cranial neural crest. PLOS Genet. 8:9e1002938 [Google Scholar]
  38. Koning L, Corpet A, Haber JE, Almouzni G. De 2007. Histone chaperones: an escort network regulating histone traffic. Nat. Struct. Mol. Biol. 14:11997–1007 [Google Scholar]
  39. de Tayrac M, Saikali S, Aubry M, Bellaud P, Boniface R. et al. 2013. Prognostic significance of EDN/RB, HJURP, p60/CAF-1 and PDLI4, four new markers in high-grade gliomas. PLOS ONE 8:9e73332 [Google Scholar]
  40. de Wilde RF, Heaphy CM, Maitra A, Meeker AK, Edil BH. et al. 2012. Loss of ATRX or DAXX expression and concomitant acquisition of the alternative lengthening of telomeres phenotype are late events in a small subset of MEN-1 syndrome pancreatic neuroendocrine tumors. Mod. Pathol. 25:71033–39 [Google Scholar]
  41. Drané P, Ouararhni K, Depaux A, Shuaib M, Hamiche A. 2010. The death-associated protein DAXX is a novel histone chaperone involved in the replication-independent deposition of H3.3. Genes Dev. 24:121253–65 [Google Scholar]
  42. Dunleavy EM, Beier NL, Gorgescu W, Tang J, Costes SV, Karpen GH. 2012. The cell cycle timing of centromeric chromatin assembly in Drosophila meiosis is distinct from mitosis yet requires CAL1 and CENP-C. PLOS Biol. 10:12e1001460 [Google Scholar]
  43. Dunleavy EM, Roche D, Tagami H, Lacoste N, Ray-Gallet D. et al. 2009. HJURP is a cell-cycle-dependent maintenance and deposition factor of CENP-A at centromeres. Cell 137:3485–97 [Google Scholar]
  44. Elsasser SJ, Huang H, Lewis PW, Chin JW, Allis CD, Patel DJ. 2012. DAXX envelops a histone H3.3-H4 dimer for H3.3-specific recognition. Nature 491:7425560–65 [Google Scholar]
  45. Erkek S, Hisano M, Liang C-Y, Gill M, Murr R. et al. 2013. Molecular determinants of nucleosome retention at CpG-rich sequences in mouse spermatozoa. Nat. Struct. Mol. Biol. 20:7868–75 [Google Scholar]
  46. Fachinetti D, Folco HD, Nechemia-Arbely Y, Valente LP, Nguyen K. et al. 2013. A two-step mechanism for epigenetic specification of centromere identity and function. Nat. Cell Biol. 15:81056–66 [Google Scholar]
  47. Filipescu D, Szenker E, Almouzni G. 2013. Developmental roles of histone H3 variants and their chaperones. Trends Genet. 29:11630–40 [Google Scholar]
  48. Foltz DR, Jansen LET, Bailey AO, Yates JR, Bassett EA. et al. 2009. Centromere-specific assembly of CENP-A nucleosomes is mediated by HJURP. Cell 137:3472–84 [Google Scholar]
  49. Fontebasso AM, Liu X-Y, Sturm D, Jabado N. 2013. Chromatin remodeling defects in pediatric and young adult glioblastoma: a tale of a variant histone 3 tail. Brain Pathol. 23:2210–16 [Google Scholar]
  50. Fontebasso AM, Papillon-Cavanagh S, Schwartzentruber J, Nikbakht H, Gerges N. et al. 2014. Recurrent somatic mutations in ACVR1 in pediatric midline high-grade astrocytoma. Nat. Genet. 46:5462–66 [Google Scholar]
  51. Franklin RE, Gosling RG. 1953. Molecular configuration in sodium thymonucleate. Nature 171:4356740–41 [Google Scholar]
  52. Franklin SG, Zweidler A. 1977. Non-allelic variants of histones 2a, 2b and 3 in mammals. Nature 266:5599273–75 [Google Scholar]
  53. Gaillard PH, Martini EM, Kaufman PD, Stillman B, Moustacchi E, Almouzni G. 1996. Chromatin assembly coupled to DNA repair: a new role for chromatin assembly factor I. Cell 86:6887–96 [Google Scholar]
  54. Garrick D, Sharpe JA, Arkell R, Dobbie L, Smith AJH. et al. 2006. Loss of Atrx affects trophoblast development and the pattern of X-inactivation in extraembryonic tissues. PLOS Genet. 2:4e58 [Google Scholar]
  55. Gaspar-Maia A, Alajem A, Polesso F, Sridharan R, Mason MJ. et al. 2009. Chd1 regulates open chromatin and pluripotency of embryonic stem cells. Nature 460:7257863–68 [Google Scholar]
  56. Gassmann R, Rechtsteiner A, Yuen KW, Muroyama A, Egelhofer T. et al. 2012. An inverse relationship to germline transcription defines centromeric chromatin in C. elegans. Nature 484:7395534–37 [Google Scholar]
  57. Gibbons RJ, Picketts DJ, Villard L, Higgs DR. 1995. Mutations in a putative global transcriptional regulator cause X-linked mental retardation with α-thalassemia (ATR-X syndrome). Cell 80:6837–45 [Google Scholar]
  58. Goldberg AD, Banaszynski LA, Noh K-M, Lewis PW, Elsäesser SJ. et al. 2010. Distinct factors control histone variant H3.3 localization at specific genomic regions. Cell 140:5678–91 [Google Scholar]
  59. Green CM, Almouzni G. 2002. When repair meets chromatin. First in series on chromatin dynamics. EMBO Rep. 3:128–33 [Google Scholar]
  60. Green CM, Almouzni G. 2003. Local action of the chromatin assembly factor CAF-1 at sites of nucleotide excision repair in vivo. EMBO J. 22:195163–74 [Google Scholar]
  61. Groth A, Corpet A, Cook AJL, Roche D, Bartek J. et al. 2007. Regulation of replication fork progression through histone supply and demand. Science 318:58581928–31 [Google Scholar]
  62. Gurard-Levin ZA, Quivy J-P, Almouzni G. 2014. Histone chaperones: assisting histone traffic and nucleosome dynamics. Annu. Rev. Biochem. 83:487–517 [Google Scholar]
  63. Hajkova P, Ancelin K, Waldmann T, Lacoste N, Lange UC. et al. 2008. Chromatin dynamics during epigenetic reprogramming in the mouse germ line. Nature 452:7189877–81 [Google Scholar]
  64. Hammoud SS, Nix DA, Zhang H, Purwar J, Carrell DT, Cairns BR. 2009. Distinctive chromatin in human sperm packages genes for embryo development. Nature 460:7254473–78 [Google Scholar]
  65. Harada A, Okada S, Konno D, Odawara J, Yoshimi T. et al. 2012. Chd2 interacts with H3.3 to determine myogenic cell fate. EMBO J. 31:132994–3007 [Google Scholar]
  66. Heitz E. 1928. Das Heterochromatin der Moose Berlin: Bornträger [Google Scholar]
  67. Hödl M, Basler K. 2009. Transcription in the absence of histone H3.3. Curr. Biol. 19:141221–26 [Google Scholar]
  68. Hödl M, Basler K. 2012. Transcription in the absence of histone H3.2 and H3K4 methylation. Curr. Biol. 22:232253–57 [Google Scholar]
  69. Houlard M, Berlivet S, Probst AV, Quivy J-P, Héry P. et al. 2006. CAF-1 is essential for heterochromatin organization in pluripotent embryonic cells. PLOS Genet. 2:11e181 [Google Scholar]
  70. Howman EV, Fowler KJ, Newson AJ, Redward S, MacDonald AC. et al. 2000. Early disruption of centromeric chromatin organization in centromere protein A (Cenpa) null mice. Proc. Natl. Acad. Sci. USA 97:31148–53 [Google Scholar]
  71. Hu Z, Huang G, Sadanandam A, Gu S, Lenburg ME. et al. 2010. The expression level of HJURP has an independent prognostic impact and predicts the sensitivity to radiotherapy in breast cancer. Breast Cancer Res. 12:2R18 [Google Scholar]
  72. Huang S, Zhou H, Katzmann D, Hochstrasser M, Atanasova E, Zhang Z. 2005. Rtt106p is a histone chaperone involved in heterochromatin-mediated silencing. Proc. Natl. Acad. Sci. USA 102:3813410–15 [Google Scholar]
  73. Jasencakova Z, Scharf AND, Ask K, Corpet A, Imhof A. et al. 2010. Replication stress interferes with histone recycling and predeposition marking of new histones. Mol. Cell 37:5736–43 [Google Scholar]
  74. Jiao Y, Shi C, Edil BH, de Wilde RF, Klimstra DS. et al. 2011. DAXX/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors. Science 331:60211199–203 [Google Scholar]
  75. Johnson BE, Mazor T, Hong C, Barnes M, Aihara K. et al. 2014. Mutational analysis reveals the origin and therapy-driven evolution of recurrent glioma. Science 343:6167189–93 [Google Scholar]
  76. Jones JM, Bhattacharyya A, Simkus C, Vallieres B, Veenstra TD, Zhou M. 2011. The RAG1 V(D)J recombinase/ubiquitin ligase promotes ubiquitylation of acetylated, phosphorylated histone 3.3. Immunol. Lett. 136:2156–62 [Google Scholar]
  77. Jullien J, Astrand C, Szenker E, Garrett N, Almouzni G, Gurdon JB. 2012. HIRA dependent H3.3 deposition is required for transcriptional reprogramming following nuclear transfer to Xenopus oocytes. Epigenet. Chromatin 5:117 [Google Scholar]
  78. Kalitsis P, Fowler KJ, Earle E, Griffiths B, Howman E. et al. 2003. Partially functional Cenpa-GFP fusion protein causes increased chromosome missegregation and apoptosis during mouse embryogenesis. Chromosome Res. 11:4345–57 [Google Scholar]
  79. Katagiri C, Ohsumi K. 1994. Remodeling of sperm chromatin induced in egg extracts of amphibians. Int. J. Dev. Biol. 38:2209–16 [Google Scholar]
  80. Kato T, Sato N, Hayama S, Yamabuki T, Ito T. et al. 2007. Activation of Holliday junction recognizing protein involved in the chromosomal stability and immortality of cancer cells. Cancer Res. 67:188544–53 [Google Scholar]
  81. Kaufman PD, Kobayashi R, Kessler N, Stillman B. 1995. The p150 and p60 subunits of chromatin assembly factor I: a molecular link between newly synthesized histones and DNA replication. Cell 81:71105–14 [Google Scholar]
  82. Kawamura M, Akiyama T, Tsukamoto S, Suzuki MG, Aoki F. 2012. The expression and nuclear deposition of histone H3.1 in murine oocytes and preimplantation embryos. J. Reprod. Dev. 58:5557–62 [Google Scholar]
  83. Khuong-Quang D-A, Buczkowicz P, Rakopoulos P, Liu X-Y, Fontebasso AM. et al. 2012. K27M mutation in histone H3.3 defines clinically and biologically distinct subgroups of pediatric diffuse intrinsic pontine gliomas. Acta Neuropathol. 124:3439–47 [Google Scholar]
  84. Kleinschmidt JA, Fortkamp E, Krohne G, Zentgraf H, Franke WW. 1985. Co-existence of two different types of soluble histone complexes in nuclei of Xenopus laevis oocytes. J. Biol. Chem. 260:21166–76 [Google Scholar]
  85. Komatsu T, Nagata K. 2012. Replication-uncoupled histone deposition during adenovirus DNA replication. J. Virol. 86:126701–11 [Google Scholar]
  86. Konev AY, Tribus M, Park SY, Podhraski V, Lim CY. et al. 2007. CHD1 motor protein is required for deposition of histone variant H3.3 into chromatin in vivo. Science 317:58411087–90 [Google Scholar]
  87. Kornberg RD. 1974. Chromatin structure: a repeating unit of histones and DNA. Science 184:4139868–71 [Google Scholar]
  88. Lacoste N, Woolfe A, Tachiwana H, Garea AV, Barth T. et al. 2014. Mislocalization of the centromeric histone variant CenH3/CENP-A in human cells depends on the chaperone DAXX. Mol. Cell 53:631–44 [Google Scholar]
  89. Latreille D, Bluy L, Benkirane M, Kiernan RE. 2014. Identification of histone 3 variant 2 interacting factors. Nucleic Acids Res. 42:3542–50 [Google Scholar]
  90. Le S, Davis C, Konopka JB, Sternglanz R. 1997. Two new S-phase-specific genes from Saccharomyces cerevisiae. Yeast 13:111029–42 [Google Scholar]
  91. Lewis PW, Elsäesser SJ, Noh K-M, Stadler SC, Allis CD. 2010. Daxx is an H3.3-specific histone chaperone and cooperates with ATRX in replication-independent chromatin assembly at telomeres. Proc. Natl. Acad. Sci. USA 107:3214075–80 [Google Scholar]
  92. Lewis PW, Müller MM, Koletsky MS, Cordero F, Lin S. et al. 2013. Inhibition of PRC2 activity by a gain-of-function H3 mutation found in pediatric glioblastoma. Science 340:6134857–61 [Google Scholar]
  93. Lim CY, Reversade B, Knowles BB, Solter D. 2013. Optimal histone H3 to linker histone H1 chromatin ratio is vital for mesodermal competence in Xenopus. Development 140:4853–60 [Google Scholar]
  94. Lin C-J, Conti M, Ramalho-Santos M. 2013. Histone variant H3.3 maintains a decondensed chromatin state essential for mouse preimplantation development. Development 140:173624–34 [Google Scholar]
  95. Liu C-P, Xiong C, Wang M, Yu Z, Yang N. et al. 2012. Structure of the variant histone H3.3-H4 heterodimer in complex with its chaperone DAXX. Nat. Struct. Mol. Biol. 19:121287–92 [Google Scholar]
  96. Loppin B, Bonnefoy E, Anselme C, Laurençon A, Karr TL, Couble P. 2005. The histone H3.3 chaperone HIRA is essential for chromatin assembly in the male pronucleus. Nat. Cell Biol. 437:70631386–90 [Google Scholar]
  97. Loyola A, Almouzni G. 2007. Marking histone H3 variants: How, when and why?. Trends Biochem. Sci. 32:9425–33 [Google Scholar]
  98. Loyola A, Bonaldi T, Roche D, Imhof A, Almouzni G. 2006. PTMs on H3 variants before chromatin assembly potentiate their final epigenetic state. Mol. Cell 24:2309–16 [Google Scholar]
  99. Loyola A, LeRoy G, Wang YH, Reinberg D. 2001. Reconstitution of recombinant chromatin establishes a requirement for histone-tail modifications during chromatin assembly and transcription. Genes Dev. 15:212837–51 [Google Scholar]
  100. Luger K, Mader AW, Richmond RK, Sargent DF, Richmond TJ. 1997. Crystal structure of the nucleosome core particle at 2.8 Å resolution. Nature 389:6648251–60 [Google Scholar]
  101. Mariño-Ramírez L, Kann MG, Shoemaker BA, Landsman D. 2005. Histone structure and nucleosome stability. Expert Rev. Proteomics 2:5719–29 [Google Scholar]
  102. Marinoni I, Kurrer AS, Vassella E, Dettmer M, Rudolph T. et al. 2014. Loss of DAXX and ATRX are associated with chromosome instability and reduced survival of patients With pancreatic neuroendocrine tumors. Gastroenterology 146:2453–55 [Google Scholar]
  103. Martini E, Roche DM, Marheineke K, Verreault A, Almouzni G. 1998. Recruitment of phosphorylated chromatin assembly factor 1 to chromatin after UV irradiation of human cells. J. Cell Biol. 143:3563–75 [Google Scholar]
  104. Mascolo M, Vecchione ML, Ilardi G, Scalvenzi M, Molea G. et al. 2010. Overexpression of chromatin assembly factor-1/p60 helps to predict the prognosis of melanoma patients. BMC Cancer 10:63 [Google Scholar]
  105. McGhee JD, Felsenfeld G. 1980. Nucleosome structure. Annu. Rev. Biochem. 49:1115–56 [Google Scholar]
  106. McGovern SL, Qi Y, Pusztai L, Symmans WF, Buchholz TA. 2012. Centromere protein-A, an essential centromere protein, is a prognostic marker for relapse in estrogen receptor-positive breast cancer. Breast Cancer Res. 14:3R72 [Google Scholar]
  107. McGregor M, Hariharan N, Joyo AY, Margolis RL, Sussman MA. 2013. CENP-A is essential for cardiac progenitor cell proliferation. Cell Cycle 13:5739–48 [Google Scholar]
  108. Mello JA, Sillje HHW, Roche DMJ, Kirschner DB, Nigg EA, Almouzni G. 2002. Human Asf1 and CAF-1 interact and synergize in a repair-coupled nucleosome assembly pathway. EMBO Rep. 3:4329–34 [Google Scholar]
  109. Michaelson JS, Bader D, Kuo F, Kozak C, Leder P. 1999. Loss of Daxx, a promiscuously interacting protein, results in extensive apoptosis in early mouse development. Genes Dev. 13:151918–23 [Google Scholar]
  110. Michod D, Bartesaghi S, Khelifi A, Bellodi C, Berliocchi L. et al. 2012. Calcium-dependent dephosphorylation of the histone chaperone DAXX regulates H3.3 loading and transcription upon neuronal activation. Neuron 74:1122–35 [Google Scholar]
  111. Moggs JG, Grandi P, Quivy J-P, Jonsson ZO, Hubscher U. et al. 2000. A CAF-1-PCNA-mediated chromatin assembly pathway triggered by sensing DNA damage. Mol. Cell. Biol. 20:41206–18 [Google Scholar]
  112. Monen J, Maddox PS, Hyndman F, Oegema K, Desai A. 2005. Differential role of CENP-A in the segregation of holocentric C. elegans chromosomes during meiosis and mitosis. Nat. Cell Biol. 7:121248–55 [Google Scholar]
  113. Müller S, Almouzni G. 2014. A network of players in H3 histone variant deposition and maintenance at centromeres. Biochim. Biophys. Acta 1839:241–50 [Google Scholar]
  114. Munakata T, Adachi N, Yokoyama N, Kuzuhara T, Horikoshi M. 2000. A human homologue of yeast anti-silencing factor has histone chaperone activity. Genes Cells 5:3221–33 [Google Scholar]
  115. Nakano S, Stillman B, Horvitz HR. 2011. Replication-coupled chromatin assembly generates a neuronal bilateral asymmetry in C. elegans. Cell 147:71525–36 [Google Scholar]
  116. Nashun B, Akiyama T, Suzuki MG, Aoki F. 2011. Dramatic replacement of histone variants during genome remodeling in nuclear-transferred embryos. Epigenetics 6:121489–97 [Google Scholar]
  117. Ng RK, Gurdon JB. 2008. Epigenetic memory of an active gene state depends on histone H3.3 incorporation into chromatin in the absence of transcription. Nat. Cell Biol. 10:1102–9 [Google Scholar]
  118. Nguyen DN, Heaphy CM, de Wilde RF, Orr BA, Odia Y. et al. 2013. Molecular and morphologic correlates of the alternative lengthening of telomeres phenotype in high-grade astrocytomas. Brain Pathol. 23:3237–43 [Google Scholar]
  119. O'Sullivan RJ, Arnoult N, Lackner DH, Oganesian L, Haggblom C. et al. 2014. Rapid induction of alternative lengthening of telomeres by depletion of the histone chaperone ASF1. Nat. Struct. Mol. Biol. 21:2167–74 [Google Scholar]
  120. Ooi SL, Priess JR, Henikoff S. 2006. Histone H3.3 variant dynamics in the germline of Caenorhabditis elegans. PLOS Genet. 2:6e97 [Google Scholar]
  121. Orsi GA, Algazeery A, Meyer RE, Capri M, Sapey-Triomphe LM. et al. 2013. Drosophila Yemanuclein and HIRA cooperate for de novo assembly of H3.3-containing nucleosomes in the male pronucleus. PLOS Genet. 9:2e1003285 [Google Scholar]
  122. Oudet P, Gross-Bellard M, Chambon P. 1975. Electron microscopic and biochemical evidence that chromatin structure is a repeating unit. Cell 4:4281–300 [Google Scholar]
  123. Palmer DK, O'Day K, Margolis RL. 1990. The centromere specific histone CENP-A is selectively retained in discrete foci in mammalian sperm nuclei. Chromosoma 100:132–36 [Google Scholar]
  124. Pan WW, Zhou JJ, Liu XM, Xu Y, Guo LJ. et al. 2013. Death domain-associated protein DAXX promotes ovarian cancer development and chemoresistance. J. Biol. Chem. 288:1913620–30 [Google Scholar]
  125. Peterson CL, Almouzni G. 2013. Nucleosome dynamics as modular systems that integrate DNA damage and repair. Cold Spring Harb. Perspect. Biol. 5:9a012658 [Google Scholar]
  126. Polo SE, Roche D, Almouzni G. 2006. New histone incorporation marks sites of UV repair in human cells. Cell 127:3481–93 [Google Scholar]
  127. Polo SE, Theocharis SE, Grandin L, Gambotti L, Antoni G. et al. 2010. Clinical significance and prognostic value of chromatin assembly factor-1 overexpression in human solid tumours. Histopathology 57:5716–24 [Google Scholar]
  128. Polo SE, Theocharis SE, Klijanienko J, Savignoni A, Asselain B. et al. 2004. Chromatin assembly factor-1, a marker of clinical value to distinguish quiescent from proliferating cells. Cancer Res. 64:72371–81 [Google Scholar]
  129. Price BD, D'Andrea AD. 2013. Chromatin remodeling at DNA double-strand breaks. Cell 152:61344–54 [Google Scholar]
  130. Probst AV, Almouzni G. 2011. Heterochromatin establishment in the context of genome-wide epigenetic reprogramming. Trends Genet. 27:5177–85 [Google Scholar]
  131. Probst AV, Okamoto I, Casanova M, El Marjou F, Le Baccon P, Almouzni G. 2010. A strand-specific burst in transcription of pericentric satellites is required for chromocenter formation and early mouse development. Dev. Cell 19:4625–38 [Google Scholar]
  132. Puschendorf M, Terranova R, Boutsma E, Mao X, Isono K-I. et al. 2008. PRC1 and Suv39h specify parental asymmetry at constitutive heterochromatin in early mouse embryos. Nat Genet. 40:4411–20 [Google Scholar]
  133. Qiu J-J, Guo J-J, Lv T-J, Jin H-Y, Ding J-X. et al. 2013. Prognostic value of centromere protein-A expression in patients with epithelial ovarian cancer. Tumor Biol. 34:52971–75 [Google Scholar]
  134. Quivy J-P, Gerard A, Cook AJL, Roche D, Almouzni G. 2008. The HP1-p150/CAF-1 interaction is required for pericentric heterochromatin replication and S-phase progression in mouse cells. Nat. Struct. Mol. Biol. 15:9972–79 [Google Scholar]
  135. Quivy J-P, Grandi P, Almouzni G. 2001. Dimerization of the largest subunit of chromatin assembly factor 1: importance in vitro and during Xenopus early development. EMBO J. 20:82015–27 [Google Scholar]
  136. Rai TS, Puri A, McBryan T, Hoffman J, Tang Y. et al. 2011. Human CABIN1 is a functional member of the human HIRA/UBN1/ASF1a histone H3.3 chaperone complex. Mol. Cell. Biol. 31:194107–18 [Google Scholar]
  137. Ray-Gallet D, Quivy J-P, Scamps C, Martini EM-D, Lipinski M, Almouzni G. 2002. HIRA is critical for a nucleosome assembly pathway independent of DNA synthesis. Mol. Cell 9:51091–100 [Google Scholar]
  138. Ray-Gallet D, Woolfe A, Vassias I, Pellentz C, Lacoste N. et al. 2011. Dynamics of histone H3 deposition in vivo reveal a nucleosome gap-filling mechanism for H3.3 to maintain chromatin integrity. Mol. Cell 44:6928–41 [Google Scholar]
  139. Raychaudhuri N, Dubruille R, Orsi GA, Bagheri HC, Loppin B, Lehner CF. 2012. Transgenerational propagation and quantitative maintenance of paternal centromeres depends on Cid/Cenp-A presence in Drosophila sperm. PLOS Biol. 10:12e1001434 [Google Scholar]
  140. Renella R, Roberts NA, Brown JM, De Gobbi M, Bird LE. et al. 2011. Codanin-1 mutations in congenital dyserythropoietic anemia type 1 affect HP1α localization in erythroblasts. Blood 117:256928–38 [Google Scholar]
  141. Richardson RT, Batova IN, Widgren EE, Zheng LX, Whitfield M. et al. 2000. Characterization of the histone H1-binding protein, NASP, as a cell cycle-regulated somatic protein. J. Biol. Chem. 275:3930378–86 [Google Scholar]
  142. Ridgway P, Brown KD, Rangasamy D, Svensson U, Tremethick DJ. 2004. Unique residues on the H2A.Z containing nucleosome surface are important for Xenopus laevis development. J. Biol. Chem. 279:4243815–20 [Google Scholar]
  143. Roberts C, Sutherland HF, Farmer H, Kimber W, Halford S. et al. 2002. Targeted mutagenesis of the Hira gene results in gastrulation defects and patterning abnormalities of mesoendodermal derivatives prior to early embryonic lethality. Mol. Cell. Biol. 22:72318–28 [Google Scholar]
  144. Rogers RS, Inselman A, Handel MA, Matunis MJ. 2004. SUMO modified proteins localize to the XY body of pachytene spermatocytes. Chromosoma 113:5233–43 [Google Scholar]
  145. Royo H, Polikiewicz G, Mahadevaiah SK, Prosser H, Mitchell M. et al. 2010. Evidence that meiotic sex chromosome inactivation is essential for male fertility. Curr. Biol. 20:232117–23 [Google Scholar]
  146. Russo V, Martienssen RA, Riggs AD. 1996. Epigenetic Mechanisms of Gene Regulation. Plainview, NY: Cold Spring Harb. Lab. Press [Google Scholar]
  147. Sakai A, Schwartz BE, Goldstein S, Ahmad K. 2009. Transcriptional and developmental functions of the H3.3 histone variant in Drosophila. Curr. Biol. 19:211816–20 [Google Scholar]
  148. Salomoni P. 2013. The PML-interacting protein DAXX: Histone loading gets into the picture. Front. Oncol. 3:152 [Google Scholar]
  149. Santenard A, Torres-Padilla M-E. 2009. Epigenetic reprogramming in mammalian reproduction: contribution from histone variants. Epigenetics 4:280–84 [Google Scholar]
  150. Santenard A, Ziegler-Birling C, Koch M, Tora L, Bannister AJ, Torres-Padilla M-E. 2010. Heterochromatin formation in the mouse embryo requires critical residues of the histone variant H3.3. Nat. Cell Biol. 12:9853–62 [Google Scholar]
  151. Sawatsubashi S, Murata T, Lim J, Fujiki R, Ito S. et al. 2010. A histone chaperone, DEK, transcriptionally coactivates a nuclear receptor. Genes Dev. 24:2159–70 [Google Scholar]
  152. Schek N, Bachenheimer SL. 1985. Degradation of cellular mRNAs induced by a virion-associated factor during herpes simplex virus infection of Vero cells. J. Virol. 55:3601–10 [Google Scholar]
  153. Schenk R, Jenke A, Zilbauer M, Wirth S, Postberg J. 2011. H3.5 is a novel hominid-specific histone H3 variant that is specifically expressed in the seminiferous tubules of human testes. Chromosoma 120:3275–85 [Google Scholar]
  154. Schneiderman JI, Orsi GA, Hughes KT, Loppin B, Ahmad K. 2012. Nucleosome-depleted chromatin gaps recruit assembly factors for the H3.3 histone variant. Proc. Natl. Acad. Sci. USA 109:4819721–26 [Google Scholar]
  155. Schuh M, Lehner CF, Heidmann S. 2007. Incorporation of Drosophila CID/CENP-A and CENP-C into centromeres during early embryonic anaphase. Curr. Biol. 17:3237–43 [Google Scholar]
  156. Schwartzentruber J, Korshunov A, Liu X-Y, Jones DTW, Pfaff E. et al. 2012. Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature 482:226–31 [Google Scholar]
  157. Shang W-H, Hori T, Martins NMC, Toyoda A, Misu S. et al. 2013. Chromosome engineering allows the efficient isolation of vertebrate neocentromeres. Dev. Cell 24:6635–48 [Google Scholar]
  158. Sharp JA, Fouts ET, Krawitz DC, Kaufman PD. 2001. Yeast histone deposition protein Asf1p requires Hir proteins and PCNA for heterochromatic silencing. Curr. Biol. 11:7463–73 [Google Scholar]
  159. Shen H, Laird PW. 2013. Interplay between the cancer genome and epigenome. Cell 153:138–55 [Google Scholar]
  160. Shen X, Ranallo R, Choi E, Wu C. 2003. Involvement of actin-related proteins in ATP-dependent chromatin remodeling. Mol. Cell 12:1147–55 [Google Scholar]
  161. Shuaib M, Ouararhni K, Dimitrov S, Hamiche A. 2010. HJURP binds CENP-A via a highly conserved N-terminal domain and mediates its deposition at centromeres. Proc. Natl. Acad. Sci. USA 107:41349–54 [Google Scholar]
  162. Skene PJ, Henikoff S. 2013. Histone variants in pluripotency and disease. Development 140:122513–24 [Google Scholar]
  163. Smeenk G, van Attikum H. 2013. The chromatin response to DNA breaks: leaving a mark on genome integrity. Annu. Rev. Biochem. 82:55–80 [Google Scholar]
  164. Smerdon MJ. 1991. DNA repair and the role of chromatin structure. Curr. Opin. Cell Biol. 3:3422–28 [Google Scholar]
  165. Smith S, Stillman B. 1989. Purification and characterization of CAF-I, a human cell factor required for chromatin assembly during DNA replication in vitro. Cell 58:115–25 [Google Scholar]
  166. Solomon LA, Li JR, Bérubé NG, Beier F. 2009. Loss of ATRX in chondrocytes has minimal effects on skeletal development. PLOS ONE 4:9e7106 [Google Scholar]
  167. Solomon LA, Russell BA, Watson LA, Beier F, Bérubé NG. 2013. Targeted loss of the ATR-X syndrome protein in the limb mesenchyme of mice causes brachydactyly. Hum. Mol. Genet. 22:245015–25 [Google Scholar]
  168. Song T-Y, Yang J-H, Park J-Y, Song Y, Han J-W. et al. 2012. The role of histone chaperones in osteoblastic differentiation of C2C12 myoblasts. Biochem. Biophys. Res. Commun. 423:4726–32 [Google Scholar]
  169. Soria G, Polo SE, Almouzni G. 2012. Prime, repair, restore: the active role of chromatin in the DNA damage response. Mol. Cell 46:6722–34 [Google Scholar]
  170. Staibano S, Mascolo M, Mancini FP, Kisslinger A, Salvatore G. et al. 2009. Overexpression of chromatin assembly factor-1 (CAF-1) p60 is predictive of adverse behaviour of prostatic cancer. Histopathology 54:5580–89 [Google Scholar]
  171. Staibano S, Mascolo M, Rocco A, Lo Muzio L, Ilardi G. et al. 2011. The proliferation marker Chromatin Assembly Factor-1 is of clinical value in predicting the biological behaviour of salivary gland tumours. Oncol. Rep. 25:113–22 [Google Scholar]
  172. Sturm D, Witt H, Hovestadt V, Khuong-Quang D-A, Jones DTW. et al. 2012. Hotspot mutations in H3F3A and IDH1 define distinct epigenetic and biological subgroups of glioblastoma. Cancer Cell 22:4425–37 [Google Scholar]
  173. Surani MA, Hayashi K, Hajkova P. 2007. Genetic and epigenetic regulators of pluripotency. Cell 128:4747–62 [Google Scholar]
  174. Szenker E, Boyarchuk E, Almouzni G. 2014. Properties and functions of histone variants. Fundamentals of Chromatin 1 JL Workman, SM Abmayr 375–426 New York: Springer, 1st. ed. [Google Scholar]
  175. Szenker E, Lacoste N, Almouzni G. 2012. A developmental requirement for HIRA-dependent H3.3 deposition revealed at gastrulation in Xenopus. Cell Rep. 1:6730–40 [Google Scholar]
  176. Szenker E, Ray-Gallet D, Almouzni G. 2011. The double face of the histone variant H3.3. Cell Res. 21:3421–34 [Google Scholar]
  177. Tachiwana H, Kagawa W, Osakabe A, Kawaguchi K, Shiga T. et al. 2010. Structural basis of instability of the nucleosome containing a testis-specific histone variant, human H3T. Proc. Natl. Acad. Sci. USA 107:2310454–59 [Google Scholar]
  178. Tagami H, Ray-Gallet D, Almouzni G, Nakatani Y. 2004. Histone H3.1 and H3.3 complexes mediate nucleosome assembly pathways dependent or independent of DNA synthesis. Cell 116:151–61 [Google Scholar]
  179. Talbert PB, Ahmad K, Almouzni G, Ausió J, Berger F. et al. 2012. A unified phylogeny-based nomenclature for histone variants. Epigenet. Chromatin 5:7 [Google Scholar]
  180. Tang MCW, Jacobs SA, Wong LH, Mann JR. 2013. Conditional allelic replacement applied to genes encoding the histone variant H3.3 in the mouse. Genesis 51:2142–46 [Google Scholar]
  181. Taylor KR, Mackay A, Truffaux N, Butterfield YS, Morozova O. et al. 2014. Recurrent activating ACVR1 mutations in diffuse intrinsic pontine glioma. Nat. Genet. 46:5457–61 [Google Scholar]
  182. Tomonaga T, Matsushita K, Yamaguchi S, Oohashi T, Shimada H. et al. 2003. Overexpression and mistargeting of centromere protein-A in human primary colorectal cancer. Cancer Res. 63:133511–16 [Google Scholar]
  183. Torres-Padilla M-E, Bannister AJ, Hurd PJ, Kouzarides T, Zernicka-Goetz M. 2006. Dynamic distribution of the replacement histone variant H3.3 in the mouse oocyte and preimplantation embryos. Int. J. Dev. Biol. 50:5455–61 [Google Scholar]
  184. Tran V, Lim C, Xie J, Chen X. 2012. Asymmetric division of Drosophila male germline stem cell shows asymmetric histone distribution. Science 338:6107679–82 [Google Scholar]
  185. Tsourlakis MC, Schoop M, Plass C, Huland H, Graefen M. et al. 2013. Overexpression of the chromatin remodeler death-domain-associated protein in prostate cancer is an independent predictor of early prostate-specific antigen recurrence. Hum. Pathol. 44:91789–96 [Google Scholar]
  186. Tyler JK, Adams CR, Chen SR, Kobayashi R, Kamakaka RT, Kadonaga JT. 1999. The RCAF complex mediates chromatin assembly during DNA replication and repair. Nature 402:6761555–60 [Google Scholar]
  187. Unhavaithaya Y, Orr-Weaver TL. 2013. Centromere proteins CENP-C and CAL1 functionally interact in meiosis for centromere clustering, pairing, and chromosome segregation. Proc. Natl. Acad. Sci. USA 110:4919878–83 [Google Scholar]
  188. Urban MK, Zweidler A. 1983. Changes in nucleosomal core histone variants during chicken development and maturation. Dev. Biol. 95:2421–28 [Google Scholar]
  189. Valente LP, Silva MCC, Jansen LET. 2012. Temporal control of epigenetic centromere specification. Chromosome Res. 20:5481–92 [Google Scholar]
  190. Valente V, Serafim RB, de Oliveira LC, Adorni FS, Torrieri R. et al. 2013. Modulation of HJURP (Holliday junction-recognizing protein) levels is correlated with glioblastoma cells survival. PLOS ONE 8:4e62200 [Google Scholar]
  191. van der Heijden GW, Derijck AAHA, Pósfai E, Giele M, Pelczar P. et al. 2007. Chromosome-wide nucleosome replacement and H3.3 incorporation during mammalian meiotic sex chromosome inactivation. Nat. Genet. 39:2251–58 [Google Scholar]
  192. van der Heijden GW, Dieker JW, Derijck AAHA, Muller S, Berden JHM. et al. 2005. Asymmetry in histone H3 variants and lysine methylation between paternal and maternal chromatin of the early mouse zygote. Mech. Dev. 122:91008–22 [Google Scholar]
  193. Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA, Kinzler KW. 2013. Cancer genome landscapes. Science 339:61271546–58 [Google Scholar]
  194. Waddington CH. 1957. The Strategy of the Genes, a Discussion of Some Aspects of Theoretical Biology. London: Allen & Unwin [Google Scholar]
  195. Wang M-Y, Guo Q-H, Du X-Z, Zhou L, Luo Q. et al. 2014. HIRA is essential for the development of gibel carp. Fish Physiol. Biochem. 40:1235–44 [Google Scholar]
  196. Watson JD, Crick FH. 1953. Molecular structure of nucleic acids: a structure for deoxyribose nucleic acid. Nature 171:4356737–38 [Google Scholar]
  197. Watson LA, Solomon LA, Li JR, Jiang Y, Edwards M. et al. 2013. Atrx deficiency induces telomere dysfunction, endocrine defects, and reduced life span. J. Clin. Investig. 123:52049–63 [Google Scholar]
  198. Woodcock CL, Ghosh RP. 2010. Chromatin higher-order structure and dynamics. Cold Spring Harb. Perspect. Biol. 2:5a000596 [Google Scholar]
  199. Wu G, Broniscer A, McEachron TA, Lu C, Paugh BS. et al. 2012a. Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas. Nat. Genet. 44:251–53 [Google Scholar]
  200. Wu G, Diaz AK, Paugh BS, Rankin SL, Ju B. et al. 2014. The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma. Nat. Genet. 46:5444–50 [Google Scholar]
  201. Wu Q, Qian Y-M, Zhao X-L, Wang S-M, Feng X-J. et al. 2012b. Expression and prognostic significance of centromere protein A in human lung adenocarcinoma. Lung Cancer 77:407–14 [Google Scholar]
  202. Yager DR, Bachenheimer SL. 1988. Synthesis and metabolism of cellular transcripts in HSV-1 infected cells. Virus Genes 1:2135–48 [Google Scholar]
  203. Yang J-H, Choi J-H, Jang H, Park J-Y, Han J-W. et al. 2011a. Histone chaperones cooperate to mediate Mef2-targeted transcriptional regulation during skeletal myogenesis. Biochem. Biophys. Res. Commun. 407:3541–47 [Google Scholar]
  204. Yang J-H, Song Y, Seol J-H, Park J-Y, Yang Y-J. et al. 2011b. Myogenic transcriptional activation of MyoD mediated by replication-independent histone deposition. Proc. Natl. Acad. Sci. USA 108:185–90 [Google Scholar]
  205. Zeitlin SG, Patel S, Kavli B, Slupphaug G. 2005. Xenopus CENP-A assembly into chromatin requires base excision repair proteins. DNA Repair 4:7760–72 [Google Scholar]
  206. Zhao Z-K, Li W, Wang M-Y, Zhou L, Wang J-L, Wang Y-F. 2011. The role of HIRA and maternal histones in sperm nucleus decondensation in the gibel carp and color crucian carp. Mol. Reprod. Dev. 78:2139–47 [Google Scholar]

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