Histone Variants and Transcription Regulation

  • Cindy Law
  • Peter CheungEmail author
Part of the Subcellular Biochemistry book series (SCBI, volume 61)


Histones are the protein components of chromatin and are important for its organization and compaction. Although core histones are exclusively expressed during S phase of the cell cycle, there exist variants of canonical histones that are expressed throughout the cell cycle. These histone variants are often deposited at defined regions of the genome and they play important roles in a variety of cellular processes, such as transcription regulation, heterochromatin formation and DNA repair. In this chapter, we will focus on several histone variants that have been linked to transcription regulation, and highlight their physical and functional features that facilitate their activities in this context.


Core Histone Histone Variant Linker Histone Heterochromatin Formation Pericentric Heterochromatin 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Abbott DW, Ivanova VS, Wang X, Bonner WM, Ausió J (2001) Characterization of the stability and folding of H2A.Z chromatin particles: implications for transcriptional activation. J Biol Chem 276:41945–41949PubMedCrossRefGoogle Scholar
  2. Abbott DW, Laszczak M, Lewis JD, Su H, Moore SC, Hills M, Dimitrov S, Ausió J (2004) Structural characterization of macroH2A containing chromatin. Biochemistry 43:1352–1359PubMedCrossRefGoogle Scholar
  3. Adam M, Robert F, Larochelle M, Gaudreau L (2001) H2A.Z is required for global chromatin integrity and for recruitment of RNA polymerase II under specific conditions. Mol Cell Biol 21:6270–6279PubMedCrossRefGoogle Scholar
  4. Agelopoulos M, Thanos D (2006) Epigenetic determination of a cell-specific gene expression program by ATF-2 and the histone variant macroH2A. EMBO J 25:4843–4853PubMedCrossRefGoogle Scholar
  5. Ahmad K, Henikoff S (2002) The histone variant H3.3 marks active chromatin by replication-independent nucleosome assembly. Mol Cell 9:1191–1200PubMedCrossRefGoogle Scholar
  6. Akhmanova AS, Bindels PC, Xu J, Miedema K, Kremer H, Hennig W (1995) Structure and expression of histone H3.3 genes in Drosophila melanogaster and Drosophila hydei. Genome 38:586–600PubMedCrossRefGoogle Scholar
  7. Alberts B (2002) Molecular biology of the cell, 4th edn. Garland Science, New YorkGoogle Scholar
  8. Albig W, Doenecke D (1997) The human histone gene cluster at the D6S105 locus. Hum Genet 101:284–294PubMedCrossRefGoogle Scholar
  9. Allis CD, Glover CV, Bowen JK, Gorovsky MA (1980) Histone variants specific to the transcriptionally active, amitotically dividing macronucleus of the unicellular eucaryote, Tetrahymena thermophila. Cell 20:609–617PubMedCrossRefGoogle Scholar
  10. Amat R, Gudas LJ (2011) RARγ is required for correct deposition and removal of Suz12 and H2A.Z in embryonic stem cells. J Cell Physiol 226:293–298PubMedCrossRefGoogle Scholar
  11. Angelov D, Molla A, Perche P-Y, Hans F, Côté J, Khochbin S, Bouvet P, Dimitrov S (2003) The histone variant macroH2A interferes with transcription factor binding and SWI/SNF nucleosome remodeling. Mol Cell 11:1033–1041PubMedCrossRefGoogle Scholar
  12. Angelov D, Verdel A, An W, Bondarenko V, Hans F, Doyen CM, Studitsky VM, Hamiche A, Roeder RG, Bouvet P, Dimitrov S (2004) SWI/SNF remodeling and p300-dependent transcription of histone variant H2ABbd nucleosomal arrays. EMBO J 23:3815–3824PubMedCrossRefGoogle Scholar
  13. Araya I, Nardocci G, Morales J, Vera M, Molina A, Alvarez M (2010) MacroH2A subtypes contribute antagonistically to the transcriptional regulation of the ribosomal cistron during seasonal acclimatization of the carp fish. Epigenetics Chromatin 3:14PubMedCrossRefGoogle Scholar
  14. Ausió J (2006) Histone variants—the structure behind the function. Brief Funct Genomic Proteomic 5:228PubMedCrossRefGoogle Scholar
  15. Banaszynski LA, Allis CD, Lewis PW (2010) Histone variants in metazoan development. Dev Cell 19:662–674PubMedCrossRefGoogle Scholar
  16. Bao Y, Konesky K, Park Y-J, Rosu S, Dyer PN, Rangasamy D, Tremethick DJ, Laybourn PJ, Luger K (2004) Nucleosomes containing the histone variant H2A.Bbd organize only 118 base pairs of DNA. EMBO J 23:3314–3324PubMedCrossRefGoogle Scholar
  17. Barski A, Cuddapah S, Cui K, Roh T-Y, Schones DE, Wang Z, Wei G, Chepelev I, Zhao K (2007) High-resolution profiling of histone methylations in the human genome. Cell 129:823–837PubMedCrossRefGoogle Scholar
  18. Beck HC, Nielsen EC, Matthiesen R, Jensen LH, Sehested M, Finn P, Grauslund M, Hansen AM, Jensen ON (2006) Quantitative proteomic analysis of post-translational modifications of human histones. Mol Cell Proteomics 5:1314–1325PubMedCrossRefGoogle Scholar
  19. Bergmann JH, Rodríguez MG, Martins NMC, Kimura H, Kelly DA, Masumoto H, Larionov V, Jansen LET, Earnshaw WC (2011) Epigenetic engineering shows H3K4me2 is required for HJURP targeting and CENP-A assembly on a synthetic human kinetochore. EMBO J 30:328–340PubMedCrossRefGoogle Scholar
  20. Braunschweig U, Hogan GJ, Pagie L, van Steensel B (2009) Histone H1 binding is inhibited by histone variant H3.3. EMBO J 28:3635–3645PubMedCrossRefGoogle Scholar
  21. Bruce K, Myers FA, Mantouvalou E, Lefevre P, Greaves I, Bonifer C, Tremethick DJ, Thorne AW, Crane-Robinson C (2005) The replacement histone H2A.Z in a hyperacetylated form is a feature of active genes in the chicken. Nucleic Acids Res 33:5633–5639PubMedCrossRefGoogle Scholar
  22. Buschbeck M, Uribesalgo I, Wibowo I, Rué P, Martin D, Gutierrez A, Morey L, Guigó R, López-Schier H, Di Croce L (2009) The histone variant macroH2A is an epigenetic regulator of key developmental genes. Nat Struct Mol Biol 16:1074–1079PubMedCrossRefGoogle Scholar
  23. Chadwick BP, Willard HF (2001a) A novel chromatin protein, distantly related to histone H2A, is largely excluded from the inactive X chromosome. J Cell Biol 152:375–384PubMedCrossRefGoogle Scholar
  24. Chadwick BP, Willard HF (2001b) Histone H2A variants and the inactive X chromosome: identification of a second macroH2A variant. Hum Mol Genet 10:1101–1113PubMedCrossRefGoogle Scholar
  25. Chakravarthy S, Gundimella SKY, Caron C, Perche P-Y, Pehrson JR, Khochbin S, Luger K (2005) Structural characterization of the histone variant macroH2A. Mol Cell Biol 25:7616–7624PubMedCrossRefGoogle Scholar
  26. Chang EY, Ferreira H, Somers J, Nusinow DA, Owen-Hughes T, Narlikar GJ (2008) MacroH2A allows ATP-dependent chromatin remodeling by SWI/SNF and ACF complexes but specifically reduces recruitment of SWI/SNF. Biochemistry 47:13726–13732PubMedCrossRefGoogle Scholar
  27. Changolkar LN, Pehrson JR (2002) Reconstitution of nucleosomes with histone macroH2A1.2. Biochemistry 41:179–184PubMedCrossRefGoogle Scholar
  28. Changolkar LN, Singh G, Cui K, Berletch JB, Zhao K, Disteche CM, Pehrson JR (2010) Genome-wide distribution of macroH2A1 histone variants in mouse liver chromatin. Mol Cell Biol 30:5473–5483PubMedCrossRefGoogle Scholar
  29. Choo JH, Kim JD, Kim J (2007) MacroH2A1 knockdown effects on the Peg3 imprinted domain. BMC Genomics 8:479PubMedCrossRefGoogle Scholar
  30. Chow C-M, Georgiou A, Szutorisz H, Maia e Silva A, Pombo A, Barahona I, Dargelos E, Canzonetta C, Dillon N (2005) Variant histone H3.3 marks promoters of transcriptionally active genes during mammalian cell division. EMBO Rep 6:354–360PubMedCrossRefGoogle Scholar
  31. Coon JJ, Ueberheide B, Syka JEP, Dryhurst DD, Ausio J, Shabanowitz J, Hunt DF (2005) Protein identification using sequential ion/ion reactions and tandem mass spectrometry. Proc Natl Acad Sci USA 102:9463–9468PubMedCrossRefGoogle Scholar
  32. Costanzi C, Pehrson JR (1998) Histone macroH2A1 is concentrated in the inactive X chromosome of female mammals. Nature 393:599–601PubMedCrossRefGoogle Scholar
  33. Costanzi C, Pehrson JR (2001) MACROH2A2, a new member of the MARCOH2A core histone family. J Biol Chem 276:21776–21784PubMedCrossRefGoogle Scholar
  34. Creyghton MP, Markoulaki S, Levine SS, Hanna J, Lodato MA, Sha K, Young RA, Jaenisch R, Boyer LA (2008) H2AZ is enriched at polycomb complex target genes in ES cells and is necessary for lineage commitment. Cell 135(4):649–661PubMedCrossRefGoogle Scholar
  35. Cuadrado A, Corrado N, Perdiguero E, Lafarga V, Muñoz-Canoves P, Nebreda AR (2010) Essential role of p18Hamlet/SRCAP-mediated histone H2A.Z chromatin incorporation in muscle differentiation. EMBO J 29:2014–2025PubMedCrossRefGoogle Scholar
  36. Daury L, Chailleux C, Bonvallet J, Trouche D (2006) Histone H3.3 deposition at E2F-regulated genes is linked to transcription. EMBO Rep 7:66–71PubMedCrossRefGoogle Scholar
  37. Delbarre E, Jacobsen BM, Reiner AH, Sorensen AL, Kuntziger T, Collas P (2010) Chromatin environment of histone variant H3. 3 revealed by quantitative imaging and genome-scale chromatin and DNA immunoprecipitation. Mol Biol Cell 21:1872PubMedCrossRefGoogle Scholar
  38. Dion MF, Kaplan T, Kim M, Buratowski S, Friedman N, Rando OJ (2007) Dynamics of replication-independent histone turnover in budding yeast. Science 315:1405–1408PubMedCrossRefGoogle Scholar
  39. Dominski Z, Marzluff WF (1999) Formation of the 3′end of histone mRNA. Gene 239:1–14PubMedCrossRefGoogle Scholar
  40. Doyen C-M, An W, Angelov D, Bondarenko V, Mietton F, Studitsky VM, Hamiche A, Roeder RG, Bouvet P, Dimitrov S (2006a) Mechanism of polymerase II transcription repression by the histone variant macroH2A. Mol Cell Biol 26:1156–1164PubMedCrossRefGoogle Scholar
  41. Doyen C-M, Montel F, Gautier T, Menoni H, Claudet C, Delacour-Larose M, Angelov D, Hamiche A, Bednar J, Faivre-Moskalenko C, Bouvet P, Dimitrov S (2006b) Dissection of the unusual structural and functional properties of the variant H2A.Bbd nucleosome. EMBO J 25:4234–4244PubMedCrossRefGoogle Scholar
  42. Draker R, Cheung P (2009) Transcriptional and epigenetic functions of histone variant H2A.Z. Biochem Cell Biol 87:19–25PubMedCrossRefGoogle Scholar
  43. Draker R, Sarcinella E, Cheung P (2011) USP10 deubiquitylates the histone variant H2A.Z and both are required for androgen receptor-mediated gene activation. Nucleic Acids Res. doi: 10.1093/nar/gkq1352
  44. 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 24:1253–1265PubMedCrossRefGoogle Scholar
  45. Faast R, Thonglairoam V, Schulz TC, Beall J, Wells JRE, Taylor H, Matthaei K, Rathjen PD, Tremethick DJ, Lyons I (2001) Histone variant H2A.Z is required for early mammalian development. Curr Biol 11:1183–1187PubMedCrossRefGoogle Scholar
  46. Fan JY, Gordon F, Luger K, Hansen JC, Tremethick DJ (2002) The essential histone variant H2A.Z regulates the equilibrium between different chromatin conformational states. Nat Struct Biol 9:172–176PubMedCrossRefGoogle Scholar
  47. Fan JY, Rangasamy D, Luger K, Tremethick DJ (2004) H2A.Z alters the nucleosome surface to promote HP1 [alpha]-mediated chromatin fiber folding. Mol Cell 16:655–661PubMedCrossRefGoogle Scholar
  48. Farris SD, Rubio ED, Moon JJ, Gombert WM, Nelson BH, Krumm A (2005) Transcription-induced chromatin remodeling at the c-myc gene involves the local exchange of histone H2A.Z. J Biol Chem 280:25298–25303PubMedCrossRefGoogle Scholar
  49. Flaus A, Rencurel C, Ferreira H, Wiechens N, Owen-Hughes T (2004) Sin mutations alter inherent nucleosome mobility. EMBO J 23:343–353PubMedCrossRefGoogle Scholar
  50. Foster ER, Downs JA (2005) Histone H2A phosphorylation in DNA double-strand break repair. FEBS J 272:3231–3240PubMedCrossRefGoogle Scholar
  51. Frank D, Doenecke D, Albig W (2003) Differential expression of human replacement and cell cycle dependent H3 histone genes. Gene 312:135–143PubMedCrossRefGoogle Scholar
  52. Gamble MJ, Frizzell KM, Yang C, Krishnakumar R, Kraus WL (2010) The histone variant macroH2A1 marks repressed autosomal chromatin, but protects a subset of its target genes from silencing. Genes Dev 24:21–32PubMedCrossRefGoogle Scholar
  53. Garrick D, Sharpe JA, Arkell R, Dobbie L, Smith AJ, Wood WG, Higgs DR, Gibbons RJ (2006) Loss of Atrx affects trophoblast development and the pattern of X-inactivation in extraembryonic tissues. PLoS Genet 2(4):e58PubMedCrossRefGoogle Scholar
  54. Gautier T, Abbott DW, Molla A, Verdel A, Ausio J, Dimitrov S (2004) Histone variant H2ABbd confers lower stability to the nucleosome. EMBO Rep 5:715–720PubMedCrossRefGoogle Scholar
  55. Gévry N, Chan HM, Laflamme L, Livingston DM, Gaudreau L (2007) p21 transcription is regulated by differential localization of histone H2A.Z. Genes Dev 21:1869–1881PubMedCrossRefGoogle Scholar
  56. Gévry N, Hardy S, Jacques P-E, Laflamme L, Svotelis A, Robert F, Gaudreau L (2009) Histone H2A.Z is essential for estrogen receptor signaling. Genes Dev 23:1522–1533PubMedCrossRefGoogle Scholar
  57. Goldberg AD, Banaszynski LA, Noh K-M, Lewis PW, Elsaesser SJ, Stadler S, Dewell S, Law M, Guo X, Li X (2010) Distinct factors control histone variant H3.3 localization at specific genomic regions. Cell 140:678–691PubMedCrossRefGoogle Scholar
  58. González-Romero R, Méndez J, Ausió J, Eirín-López JM (2008) Quickly evolving histones, nucleosome stability and chromatin folding: all about histone H2A.Bbd. Gene 413:1–7PubMedCrossRefGoogle Scholar
  59. Gorovsky MA (1996) Essential and nonessential histone H2A variants in Tetrahymena thermophila. Mol Cell Biol 16:4305–4311Google Scholar
  60. Guillemette B, Bataille AR, Gévry N, Adam M, Blanchette M, Robert F, Gaudreau L (2005) Variant histone H2A.Z is globally localized to the promoters of inactive yeast genes and regulates nucleosome positioning. PLoS Biol 3:e384PubMedCrossRefGoogle Scholar
  61. Hake SB, Allis CD (2006) Histone H3 variants and their potential role in indexing mammalian genomes: the “H3 barcode hypothesis”. Proc Natl Acad Sci USA 103:6428–6435PubMedCrossRefGoogle Scholar
  62. Hake SB, Garcia BA, Duncan EM, Kauer M, Dellaire G, Shabanowitz J, Bazett-Jones DP, Allis CD, Hunt DF (2005) Expression patterns and post-translational modifications associated with mammalian histone H3 variants. J Biol Chem 281:559–568PubMedCrossRefGoogle Scholar
  63. Hake SB, Garcia BA, Duncan EM, Kauer M, Dellaire G, Shabanowitz J, Bazett-Jones DP, Allis CD, Hunt DF (2006) Expression patterns and post-translational modifications associated with mammalian histone H3 variants. J Biol Chem 281:559–568PubMedCrossRefGoogle Scholar
  64. Hardy S, Jacques P-E, Gévry N, Forest A, Fortin M-E, Laflamme L, Gaudreau L, Robert F (2009) The euchromatic and heterochromatic landscapes are shaped by antagonizing effects of transcription on H2A.Z deposition. PLoS Genet 5:e1000687PubMedCrossRefGoogle Scholar
  65. Harris ME, Bohni R, Schneiderman MH, Ramamurthy L, Schumperli D, Marzluff WF (1991) Regulation of histone mRNA in the unperturbed cell cycle: evidence suggesting control at two posttranscriptional steps. Mol Cell Biol 11:2416PubMedGoogle Scholar
  66. Henikoff S, Ahmad K (2005) Assembly of variant histones into chromatin. Annu Rev Cell Dev Biol 21:133–153PubMedCrossRefGoogle Scholar
  67. Hua S, Kallen CB, Dhar R, Baquero MT, Mason CE, Russell BA, Shah PK, Liu J, Khramtsov A, Tretiakova MS, Krausz TN, Olopade OI, Rimm DL, White KP (2008) Genomic analysis of estrogen cascade reveals histone variant H2A.Z associated with breast cancer progression. Mol Syst Biol 4:188PubMedCrossRefGoogle Scholar
  68. Iouzalen N, Moreau J, Méchali M (1996) H2A.ZI, a new variant histone expressed during Xenopus early development exhibits several distinct features from the core histone H2A. Nucleic Acids Res 24:3947–3952PubMedCrossRefGoogle Scholar
  69. Jackson JD, Gorovsky MA (2000) Histone H2A.Z has a conserved function that is distinct from that of the major H2A sequence variants. Nucleic Acids Res 28:3811–3816PubMedCrossRefGoogle Scholar
  70. Jin C, Felsenfeld G (2007) Nucleosome stability mediated by histone variants H3.3 and H2A.Z. Genes Dev 21:1519–1529PubMedCrossRefGoogle Scholar
  71. Jin C, Zang C, Wei G, Cui K, Peng W, Zhao K, Felsenfeld G (2009) H3.3/H2A.Z double variant-containing nucleosomes mark “nucleosome-free regions” of active promoters and other regulatory regions. Nat Genet 41:941–945PubMedCrossRefGoogle Scholar
  72. Jufvas Å, Strålfors P, Vener AV (2011) Histone variants and their post-translational modifications in primary human fat cells. PLoS One 6:e15960PubMedCrossRefGoogle Scholar
  73. Kamakaka RT (2005) Histone variants: deviants? Genes Dev 19:295–316PubMedCrossRefGoogle Scholar
  74. Kapoor A, Goldberg MS, Cumberland LK, Ratnakumar K, Segura MF, Emanuel PO, Menendez S, Vardabasso C, Leroy G, Vidal CI, Polsky D, Osman I, Garcia BA, Hernando E, Bernstein E (2010) The histone variant macroH2A suppresses melanoma progression through regulation of CDK8. Nature 468:1105–1109PubMedCrossRefGoogle Scholar
  75. Kobor MS, Venkatasubrahmanyam S, Meneghini MD, Gin JW, Jennings JL, Link AJ, Madhani HD, Rine J (2004) A protein complex containing the conserved Swi2/Snf2-related ATPase Swr1p deposits histone variant H2A.Z into euchromatin. PLoS Biol 2:E131PubMedCrossRefGoogle Scholar
  76. Kornberg RD (1974) Chromatin structure: a repeating unit of histones and DNA. Science 184:868–871PubMedCrossRefGoogle Scholar
  77. Kouzarides T (2007) Chromatin modifications and their function. Cell 128:693–705PubMedCrossRefGoogle Scholar
  78. Lewis PW, Elsaesser 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 107:14075–14080PubMedCrossRefGoogle Scholar
  79. Li B, Pattenden SG, Lee D, Gutiérrez J, Chen J, Seidel C, Gerton J, Workman JL (2005) Preferential occupancy of histone variant H2AZ at inactive promoters influences local histone modifications and chromatin remodeling. Proc Natl Acad Sci USA 102:18385–18390PubMedCrossRefGoogle Scholar
  80. 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 24:309–316PubMedCrossRefGoogle Scholar
  81. Luk E, Ranjan A, FitzGerald PC, Mizuguchi G, Huang Y, Wei D, Wu C (2010) Stepwise histone replacement by SWR1 requires dual activation with histone H2A.Z and canonical nucleosome. Cell 143:725–736PubMedCrossRefGoogle Scholar
  82. Lusser A, Kadonaga JT (2003) Chromatin remodeling by ATP-dependent molecular machines. Bioessays 25:1192–1200PubMedCrossRefGoogle Scholar
  83. Marzluff WF, Gongidi P, Woods KR, Jin J, Maltais LJ (2002) The human and mouse replication-dependent histone genes. Genomics 80:487–498PubMedCrossRefGoogle Scholar
  84. McKittrick E, Gafken PR, Ahmad K, Henikoff S (2004) Histone H3.3 is enriched in covalent modifications associated with active chromatin. Proc Natl Acad Sci USA 101:1525–1530PubMedCrossRefGoogle Scholar
  85. Meneghini MD, Wu M, Madhani HD (2003) Conserved histone variant H2A.Z protects euchromatin from the ectopic spread of silent heterochromatin. Cell 112:725–736PubMedCrossRefGoogle Scholar
  86. 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 13:1918–1923PubMedCrossRefGoogle Scholar
  87. Millar CB, Xu F, Zhang K, Grunstein M (2006) Acetylation of H2AZ Lys 14 is associated with genome-wide gene activity in yeast. Genes Dev 20:711–722PubMedCrossRefGoogle Scholar
  88. Mito Y, Henikoff JG, Henikoff S (2005) Genome-scale profiling of histone H3.3 replacement patterns. Nat Genet 37:1090–1097PubMedCrossRefGoogle Scholar
  89. Nagaki K, Cheng Z, Ouyang S, Talbert PB, Kim M, Jones KM, Henikoff S, Buell CR, Jiang J (2004) Sequencing of a rice centromere uncovers active genes. Nat Genet 36:138–145PubMedCrossRefGoogle Scholar
  90. Ng K, Pullirsch D, Leeb M, Wutz A (2007) Xist and the order of silencing. EMBO Rep 8:34–39PubMedCrossRefGoogle Scholar
  91. Nusinow DA, Hernandez-Munoz I, Fazzio TG, Shah GM, Kraus WL, Panning B (2007) Poly(ADP-ribose) polymerase 1 is inhibited by a histone H2A variant, macroH2A, and contributes to silencing of the inactive X chromosome. J Biol Chem 282:12851–12859PubMedCrossRefGoogle Scholar
  92. Ooi SL, Henikoff JG, Henikoff S (2010) A native chromatin purification system for epigenomic profiling in Caenorhabditis elegans. Nucleic Acids Res 38:e26PubMedCrossRefGoogle Scholar
  93. Osley MA (1991) The regulation of histone synthesis in the cell cycle. Annu Rev Biochem 60:827–861PubMedCrossRefGoogle Scholar
  94. Ouararhni K, Hadj-Slimane R, Ait-Si-Ali S, Robin P, Mietton F, Harel-Bellan A, Dimitrov S, Hamiche A (2006) The histone variant mH2A1.1 interferes with transcription by down-regulating PARP-1 enzymatic activity. Genes Dev 20:3324–3336PubMedCrossRefGoogle Scholar
  95. Pehrson JR, Fried VA (1992) MacroH2A, a core histone containing a large nonhistone region. Science 257:1398–1400PubMedCrossRefGoogle Scholar
  96. Placek BJ, Huang J, Kent JR, Dorsey J, Rice L, Fraser NW, Berger SL (2009) The histone variant H3.3 regulates gene expression during lytic infection with herpes simplex virus type 1. J Virol 83:1416–1421PubMedCrossRefGoogle Scholar
  97. Pusarla RH, Bhargava P (2005) Histones in functional diversification. FEBS J 272:5149–5168PubMedCrossRefGoogle Scholar
  98. Rangasamy D, Berven L, Ridgway P, Tremethick DJ (2003) Pericentric heterochromatin becomes enriched with H2A.Z during early mammalian development. EMBO J 22:1599–1607PubMedCrossRefGoogle Scholar
  99. Rhodes DR, Yu J, Shanker K, Deshpande N, Varambally R, Ghosh D, Barrette T, Pandey A, Chinnaiyan AM (2004) Large-scale meta-analysis of cancer microarray data identifies common transcriptional profiles of neoplastic transformation and progression. Proc Natl Acad Sci USA 101:9309–9314PubMedCrossRefGoogle Scholar
  100. Roberts C, Sutherland HF, Farmer H, Kimber W, Halford S, Carey A, Brickman JM, Wynshaw-Boris A, Scambler PJ (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 22:2318–2328PubMedCrossRefGoogle Scholar
  101. Rogakou EP, Pilch DR, Orr AH, Ivanova VS, Bonner WM (1998) DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139. J Biol Chem 273:5858PubMedCrossRefGoogle Scholar
  102. 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 12:853–862PubMedCrossRefGoogle Scholar
  103. Santisteban MS, Kalashnikova T, Smith MM (2000) Histone H2A.Z regulates transcription and is partially redundant with nucleosome remodeling complexes. Cell 103:411–422PubMedCrossRefGoogle Scholar
  104. Santisteban MS, Hang M, Smith MM (2011) Histone variant H2A.Z and RNA polymerase II transcription elongation. Mol Cell Biol 31:1848–1860PubMedCrossRefGoogle Scholar
  105. Sarcinella E, Zuzarte PC, Lau PNI, Draker R, Cheung P (2007) Monoubiquitylation of H2A.Z distinguishes its association with euchromatin or facultative heterochromatin. Mol Cell Biol 27:6457–6468PubMedCrossRefGoogle Scholar
  106. 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. doi: 10.1007/s00412-011-0310-4
  107. Schwartz BE, Ahmad K (2005) Transcriptional activation triggers deposition and removal of the histone variant H3.3. Genes Dev 19:804–814PubMedCrossRefGoogle Scholar
  108. Shukla MS, Syed SH, Goutte-Gattat D, Richard JLC, Montel F, Hamiche A, Travers A, Faivre-Moskalenko C, Bednar J, Hayes JJ, Angelov D, Dimitrov S (2010) The docking domain of histone H2A is required for H1 binding and RSC-mediated nucleosome remodeling. Nucleic Acids Res 39:2559–2570PubMedCrossRefGoogle Scholar
  109. Slupianek A, Yerrum S, Safadi FF, Monroy MA (2010) The chromatin remodeling factor SRCAP modulates expression of prostate specific antigen and cellular proliferation in prostate cancer cells. J Cell Physiol 224:369–375PubMedCrossRefGoogle Scholar
  110. Sporn JC, Kustatscher G, Hothorn T, Collado M, Serrano M, Muley T, Schnabel P, Ladurner AG (2009) Histone macroH2A isoforms predict the risk of lung cancer recurrence. Oncogene 28:3423–3428PubMedCrossRefGoogle Scholar
  111. Strahl BD, Allis CD (2000) The language of covalent histone modifications. Nature 403:41–45PubMedCrossRefGoogle Scholar
  112. Sullivan KF, Hechenberger M, Masri K (1994) Human CENP-A contains a histone H3 related histone fold domain that is required for targeting to the centromere. J Cell Biol 127:581PubMedCrossRefGoogle Scholar
  113. Sutcliffe EL, Parish IA, He YQ, Juelich T, Tierney ML, Rangasamy D, Milburn PJ, Parish CR, Tremethick DJ, Rao S (2009) Dynamic histone variant exchange accompanies gene induction in T cells. Mol Cell Biol 29:1972–1986PubMedCrossRefGoogle Scholar
  114. Suto RK, Clarkson MJ, Tremethick DJ, Luger K (2000) Crystal structure of a nucleosome core particle containing the variant histone H2A.Z. Nat Struct Biol 7:1121–1124PubMedCrossRefGoogle Scholar
  115. Svotelis A, Gévry N, Grondin G, Gaudreau L (2010) H2A.Z overexpression promotes cellular proliferation of breast cancer cells. Cell Cycle 9:364–370PubMedCrossRefGoogle Scholar
  116. Szenker E, Ray-Gallet D, Almouzni G (2011) The double face of the histone variant H3.3. Cell Res 21:421–434PubMedCrossRefGoogle Scholar
  117. 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 116:51–61PubMedCrossRefGoogle Scholar
  118. Talbert PB, Henikoff S (2010) Histone variants–ancient wrap artists of the epigenome. Nat Rev Mol Cell Biol 11:264–275PubMedCrossRefGoogle Scholar
  119. Tamura T, Smith M, Kanno T, Dasenbrock H, Nishiyama A, Ozato K (2009) Inducible deposition of the histone variant H3.3 in interferon-stimulated genes. J Biol Chem 284:12217–12225PubMedCrossRefGoogle Scholar
  120. Taverna SD, Li H, Ruthenburg AJ, Allis CD, Patel DJ (2007) How chromatin-binding modules interpret histone modifications: lessons from professional pocket pickers. Nat Struct Mol Biol 14:1025–1040PubMedCrossRefGoogle Scholar
  121. Thakar A, Gupta P, Ishibashi T, Finn R, Silva-Moreno B, Uchiyama S, Fukui K, Tomschik M, Ausio J, Zlatanova J (2009) H2A.Z and H3.3 histone variants affect nucleosome structure: biochemical and biophysical studies. Biochemistry 48:10852–10857PubMedCrossRefGoogle Scholar
  122. Thiriet C, Hayes JJ (2005) Chromatin in need of a fix: phosphorylation of H2AX connects chromatin to DNA repair. Mol Cell 18:617–622PubMedCrossRefGoogle Scholar
  123. Tulin A, Stewart D, Spradling AC (2002) The Drosophila heterochromatic gene encoding poly(ADP-ribose) polymerase (PARP) is required to modulate chromatin structure during development. Genes Dev 16:2108–2119PubMedCrossRefGoogle Scholar
  124. Updike DL, Mango SE (2006) Temporal regulation of foregut development by HTZ-1/H2A.Z and PHA-4/FoxA. PLoS Genet 2:e161PubMedCrossRefGoogle Scholar
  125. van Daal A, Elgin SC (1992) A histone variant, H2AvD, is essential in Drosophila melanogaster. Mol Biol Cell 3:593–602PubMedGoogle Scholar
  126. Weber CM, Henikoff JG, Henikoff S (2010) H2A.Z nucleosomes enriched over active genes are homotypic. Nat Struct Mol Biol 17:1500–1507Google Scholar
  127. Wirbelauer C, Bell O, Schübeler D (2005) Variant histone H3.3 is deposited at sites of nucleosomal displacement throughout transcribed genes while active histone modifications show a promoter-proximal bias. Genes Dev 19:1761–1766PubMedCrossRefGoogle Scholar
  128. Wong MM, Cox LK, Chrivia JC (2007) The chromatin remodeling protein, SRCAP, is critical for deposition of the histone variant H2A.Z at promoters. J Biol Chem 282:26132–26139PubMedCrossRefGoogle Scholar
  129. Wong LH, Ren H, Williams E, McGhie J, Ahn S, Sim M, Tam A, Earle E, Anderson MA, Mann J, Choo KHA (2009) Histone H3.3 incorporation provides a unique and functionally essential telomeric chromatin in embryonic stem cells. Genome Res 19:404–414PubMedCrossRefGoogle Scholar
  130. Yan H, Ito H, Nobuta K, Ouyang S, Jin W, Tian S, Lu C, Venu RC, Wang G-L, Green PJ, Wing RA, Buell CR, Meyers BC, Jiang J (2006) Genomic and genetic characterization of rice Cen3 reveals extensive transcription and evolutionary implications of a complex centromere. Plant Cell 18:2123–2133PubMedCrossRefGoogle Scholar
  131. Zhang H, Roberts DN, Cairns BR (2005a) Genome-wide dynamics of Htz1, a histone H2A variant that poises repressed/basal promoters for activation through histone loss. Cell 123:219–231PubMedCrossRefGoogle Scholar
  132. Zhang R, Poustovoitov MV, Ye X, Santos HA, Chen W, Daganzo SM, Erzberger JP, Serebriiskii IG, Canutescu AA, Dunbrack RL (2005b) Formation of MacroH2A-containing senescence-associated heterochromatin foci and senescence driven by ASF1a and HIRA. Dev Cell 8:19–30PubMedCrossRefGoogle Scholar
  133. Zhou J, Fan JY, Rangasamy D, Tremethick DJ (2007) The nucleosome surface regulates chromatin compaction and couples it with transcriptional repression. Nat Struct Mol Biol 14:1070–1076PubMedCrossRefGoogle Scholar
  134. Zilberman D, Coleman-Derr D, Ballinger T, Henikoff S (2008) Histone H2A.Z and DNA methylation are mutually antagonistic chromatin marks. Nature 456:125–129PubMedCrossRefGoogle Scholar
  135. Zlatanova J, Thakar A (2008) H2A.Z: view from the top. Structure 16:166–179PubMedCrossRefGoogle Scholar
  136. Zucchi I, Mento E, Kuznetsov VA, Scotti M, Valsecchi V, Simionati B, Vicinanza E, Valle G, Pilotti S, Reinbold R, Vezzoni P, Albertini A, Dulbecco R (2004) Gene expression profiles of epithelial cells microscopically isolated from a breast-invasive ductal carcinoma and a nodal metastasis. Proc Natl Acad Sci USA 101:18147–18152PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  1. 1.Ontario Cancer InstituteTorontoCanada
  2. 2.Department of Medical BiophysicsUniversity of TorontoTorontoCanada

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