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Histone variants: key players of chromatin

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Abstract

Histones are fundamental structural components of chromatin. Eukaryotic DNA is wound around an octamer of the core histones H2A, H2B, H3, and H4. Binding of linker histone H1 promotes higher order chromatin organization. In addition to their structural role, histones impact chromatin function and dynamics by, e.g., post-translational histone modifications or the presence of specific histone variants. Histone variants exhibit differential expression timings (DNA replication-independent) and mRNA characteristics compared to canonical histones. Replacement of canonical histones with histone variants can affect nucleosome stability and help to create functionally distinct chromatin domains. In line with this, several histone variants have been implicated in the regulation of cellular processes such as DNA repair and transcriptional activity. In this review, we focus on recent progress in the study of core histone variants H2A.X, H2A.Z, macroH2A, H3.3, and CENP-A, as well as linker histone H1 variants, their functions and their links to development and disease.

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References

  • Ahmad K, Henikoff S (2002) The histone variant H3.3 marks active chromatin by replication-independent nucleosome assembly. Mol Cell 9(6):1191–1200

    CAS  PubMed  Google Scholar 

  • Albig W, Doenecke D (1997) The human histone gene cluster at the D6S105 locus. Hum Genet 101:284–294

    CAS  PubMed  Google Scholar 

  • Amor DJ, Kalitsis P, Sumer H, Choo KH (2004) Building the centromere: from foundation proteins to 3D organization. Trends Cell Biol 14(7):359–368

    CAS  PubMed  Google Scholar 

  • Angelov D, Molla A, Perche PY, Hans F, Cote J, Khochbin S, Bouvet P, Dimitrov S (2003) The histone variant macroH2A interferes with transcription factor binding and SWI/SNF nucleosome remodeling. Mol Cell 11:1033–1041

    CAS  PubMed  Google Scholar 

  • Azuara V, Perry P, Sauer S, Spivakov M, Jorgensen HF, John RM, Gouti M, Casanova M, Warnes G, Merkenschlager M, Fisher AG (2006) Chromatin signatures of pluripotent cell lines. Nat Cell Biol 8(5):532–538

    CAS  PubMed  Google Scholar 

  • Bailey AO, Panchenko T, Sathyan KM, Petkowski JJ, Pai PJ, Bai DL, Russell DH, Macara IG, Shabanowitz J, Hunt DF, Black BE, Foltz DR (2013) Posttranslational modification of CENP-A influences the conformation of centromeric chromatin. Proc Natl Acad Sci USA 110(29):11827–11832

    CAS  PubMed Central  PubMed  Google Scholar 

  • Barrero MJ, Sesé B, Kuebler B, Bilic J, Boue S, Martí M, Izpisua Belomonte JC (2013) Macrohistone variants preserve cell identity by preventing the gain of H3K4me2 during reprogramming to pluripotency. Cell Rep S2211–1247, 105–8

  • Binda O, Sevilla A, LeRoy G, Lemischka IR, Garcia BA, Richard S (2013) SETD6 monomethylates H2AZ on lysine 7 and is required for the maintenance of embryonic stem cell self-renewal. Epigenetics 8(2):177–183

    CAS  PubMed Central  PubMed  Google Scholar 

  • Buschbeck M, Uribesalgo I, Wibowo I, Rue P, Martin D, Gutierrez A, Morey L, Guigo R, Lopez-Schier H, Di Croce L (2009) The histone variant macroH2A is an epigenetic regulator of key developmental genes. Nat Struct Mol Biol 16(10):1074–1079

    CAS  PubMed  Google Scholar 

  • Chadwick BP, Willard HF (2001) Histone H2A variants and the inactive X chromosome: identification of a second macroH2A variant. Hum Mol Genet 10(10):1101–1113

    CAS  PubMed  Google Scholar 

  • Chakravarthy S, Gundimella SK, Caron C, Perche PY, Pehrson JR, Khochbin S, Luger K (2005) Structural characterization of the histone variant macroH2A. Mol Cell Biol 25:7616–7624

    CAS  PubMed Central  PubMed  Google Scholar 

  • Chakravarthy S, Luger K (2006) The histone variant macro-H2A preferentially forms “hybrid nucleosomes”. J Biol Chem 281:25522–25531

    CAS  PubMed  Google Scholar 

  • Chan KM, Fang D, Gan H, Hashizume R, Yu C, Schroeder M, Gupta N, Mueller S, James CD, Jenkins R, Sarkaria J, Zhang Z (2013) The histone H3.3K27M mutation in pediatric glioma reprograms H3K27 methylation and gene expression. Genes Dev 27(9):985–990

    CAS  PubMed Central  PubMed  Google Scholar 

  • Changolkar LN, Pehrson JR (2002) Reconstitution of nucleosomes with histone macroH2A1.2. Biochemistry 41:179–184

    CAS  PubMed  Google Scholar 

  • Chen P, Zhao J, Li G (2013a) Histone variants in development and diseases. J Genet Genomics 40(7):355–365

    CAS  PubMed  Google Scholar 

  • Chen P, Zhao J, Wang Y, Wang M, Long H, Liang D, Huang L, Wen Z, Li W, Li X, Feng H, Zhao H, Zhu P, Li M, Wang QF, Li G (2013b) H3.3 actively marks enhancers and primes gene transcription via opening higher-ordered chromatin. Genes Dev 27(19):2109–2124

    CAS  PubMed Central  PubMed  Google Scholar 

  • Choi JK, Howe LJ (2009) Histone acetylation: truth of consequences? Biochem Cell Biol 87(1):139–150

    CAS  PubMed  Google Scholar 

  • Choo JH, Kim JD, Chung JH, Stubbs L, Kim J (2006) Allele-specific deposition of macroH2A1 in imprinting control regions. Hum Mol Genet 15:717–724

    CAS  PubMed  Google Scholar 

  • Chowdhury D, Keogh MC, Ishii H, Peterson CL, Buratowski S, Lieberman J (2005) Gamma-H2AX dephosphorylation by protein phosphatase 2A facilitates DNA double-strand break repair. Mol Cell 20:801–809

    CAS  PubMed  Google Scholar 

  • Codomo CA, Furuyama T, Henikoff S (2014) CENP-A octamers do not confer a reduction in nucleosome height by AFM. Nat Struct Mol Biol 21(1):4–5

    CAS  PubMed  Google Scholar 

  • Cook PJ, Ju BG, Telese F, Wang X, Glass CK, Rosenfeld MG (2009) Tyrosine dephosphorylation of H2AX modulates apoptosis and survival decisions. Nature 458:591–596

    CAS  PubMed Central  PubMed  Google Scholar 

  • Corpet A, Olbrich T, Gwerder M, Fink D, Stucki M (2013) Dynamics of histone H3.3 deposition in proliferating and senescent cells reveals a DAXX-dependent targeting to PML-NBs important for pericentromeric heterochromatin organization. Cell Cycle 13(2)

  • Costanzi C, Pehrson JR (1998) Histone macroH2A1 is concentrated in the inactive X chromosome of female mammals. Nature 393:599–601

    CAS  PubMed  Google Scholar 

  • Creppe C, Janich P, Cantarino N, Noguera M, Valero V, Musulen E, Douet J, Posavec M, Martin-Caballero J, Sumoy L, Di Croce L, Benitah SA, Buschbeck M (2012) MacroH2A1 regulates the balance between self-renewal and differentiation commitment in embryonic and adult stem cells. Mol Cell Biol 32(8):1442–1452

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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):649–661

    CAS  PubMed Central  PubMed  Google Scholar 

  • Dalal Y, Wang H, Lindsay S, Henikoff S (2007) Tetrameric structure of centromeric nucleosomes in interphase Drosophila cells. PLoS Biol 5(8):e218

    PubMed Central  PubMed  Google Scholar 

  • Dimitriadis EK, Weber C, Gill RK, Diekmann S, Dalal Y (2010) Tetrameric organization of vertebrate centromeric nucleosomes. Proc Natl Acad Sci USA 107(47):20317–20322

    CAS  PubMed Central  PubMed  Google Scholar 

  • Doenecke D, Drabent B, Bode C, Bramlage B, Franke K, Gavenis K, Kosciessa U, Witt O (1997) Histone gene expression and chromatin structure during spermatogenesis. Adv Exp Med Biol 424:37

    CAS  PubMed  Google Scholar 

  • Dominski Z, Marzluff WF (1999) Formation of the 3 end of histone mRNA. Gene 239:1–14

    CAS  PubMed  Google Scholar 

  • Doyen CM, An W, Angelov D, Bondarenko V, Mietton F, Studitsky VM, Hamiche A, Roeder RG, Bouvet P, Dimitrov S (2006) Mechanism of polymerase II transcription repression by the histone variant macroH2A. Mol Cell Biol 26:1156–1164

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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 24:1253–1265

    PubMed Central  PubMed  Google Scholar 

  • Dunleavy EM, Roche D, Tagami H, Lacoste N, Ray-Gallet D, Nakamura Y, Daigo Y, Nakatani Y, Almouzni-Pettinotti G (2009) HJURP is a cell-cycle-dependent maintenance and deposition factor of CENP-A at centromeres. Cell 137(3):485–497

    CAS  PubMed  Google Scholar 

  • Elsässer SJ, Allis CD (2010) HIRA and Daxx constitute two independent histone H3.3-containing predeposition complexes. Cold Spring Harb Symp Quant Biol 75:27–34

    Google Scholar 

  • Elsässer 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(7425):560–565

    PubMed  Google Scholar 

  • Faast R, Thonglairoam V, Schulz TC, Beall J, Wells JR, Taylor H, Matthaei K, Rathjen PD, Tremethick DJ, Lyons I (2001) Histone variant H2A.Z is required for early mammalian development. Curr Biol 11(15):1183–1187

    CAS  PubMed  Google Scholar 

  • Fan Y, Sirotkin A, Russel IRG, Ayala J, Skoultchi AI (2001) Individual somatic H1 subtypes are dispensable for mouse development even in mice lacking the H1(0) replacement subtype. Mol Cell Biol 21:7933–7943

    CAS  PubMed Central  PubMed  Google Scholar 

  • Fan Y, Nikitina T, Zhao J, Fleury TJ, Bhattacharyya R, Bouhassira EE, Stein A, Woodcock CL, Skoultchi AI (2005) Histone h1 depletion in mammals alters global chromatin structure but causes specific changes in gene regulation. Cell 123:1199–1212

    CAS  PubMed  Google Scholar 

  • Ferbeyre G, de Stanchina E, Querido E, Baptiste N, Prives C, Lowe SW (2000) PML is induced by oncogenic ras and promotes premature senescence. Genes Dev 14:2015–2027

    CAS  PubMed Central  PubMed  Google Scholar 

  • Fink M, Imholz D, Thoma F (2007) Contribution of the serine 129 of histone H2A to chromatin structure. Mol Cell Biol 27:3589–3600

    CAS  PubMed Central  PubMed  Google Scholar 

  • Foltz DR, Jansen LET, Bailey AO, Yates JR, Bassett EA, Wood S, Black BE, Cleveland DW (2009) Centromere-specific assembly of CENP-a nucleosomes is mediated by HJURP. Cell 137:472–484

    CAS  PubMed Central  PubMed  Google Scholar 

  • Funayama R, Saito M, Tanobe H, Ishikawa F (2006) Loss of linker histone H1 in cellular senescence. J Cell Biol 175:869–880

    CAS  PubMed Central  PubMed  Google Scholar 

  • Furuya M, Tanaka M, Teranishi T, Matsumoto K, Hosoi Y, Saeki K, Ishimoto H, Minegishi K, Iritani A, Yoshimura Y (2007) H1foo is indispensable for meiotic maturation of the mouse oocyte. J Reprod Dev 53(4):895–902

    CAS  PubMed  Google Scholar 

  • 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 24:21–32

    CAS  PubMed Central  PubMed  Google Scholar 

  • Gaspar-Maia A, Qadeer ZA, Hasson D, Ratnakumar K, Leu NA, Leroy G, Liu S, Costanzi C, Valle-Garcia D, Schaniel C, Lemischka I, Garcia B, Pehrson JR, Bernstein E (2013) MacroH2A histone variants act as a barrier upon reprogramming towards pluripotency. Nat Commun 4:1565

    PubMed  Google Scholar 

  • Goldberg AD, Banaszynski LA, Noh KM, Lewis PW, Elsaesser SJ, Stadler S, Dewell S, Law M, Guo X, Li X, Wen D, Chapgier A, DeKelver RC, Miller JC, Lee YL, Boydston EA, Holmes MC, Gregory PD, Greally JM, Rafii S, Yang C, Scambler PJ, Garrick D, Gibbons RJ, Higgs DR, Cristea IM, Urnov FD, Zheng D, Allis CD (2010) Distinct factors control histone variant H3.3 localization at specific genomic regions. Cell 140:678–691

    CAS  PubMed Central  PubMed  Google Scholar 

  • Goutte-Gattat D, Shuaib M, Ouararhni K, Gautier T, Skoufias DA, Hamiche A, Dimitrov S (2013) Phosphorylation of the CENP-A amino-terminus in mitotic centromeric chromatin is required for kinetochore function. Proc Natl Acad Sci USA 110(21):8579–8584

    CAS  PubMed Central  PubMed  Google Scholar 

  • Greaves IK, Rangasamy D, Ridgway P, Tremethick DJ (2007) H2A.Z contributes to the unique 3D structure of the centromere. Proc Natl Acad Sci USA 104:e525–e530

    Google Scholar 

  • Hake SB, Garcia BA, Kauer M, Baker SP, Shabanowitz J, Hunt DF, Allis CD (2005) Serine 31 phosphorylation of histone variant H3.3 is specific to regions bordering centromeres in metaphase chromosomes. Proc Natl Acad Sci USA 102(18):6344–6349

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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(17):6428–6435

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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(1):559–568

    CAS  PubMed  Google Scholar 

  • Happel N, Schulze E, Doenecke D (2005) Characterization of human histone H1x. Biol Chem 386:541–551

    CAS  PubMed  Google Scholar 

  • Harshman SW, Young NL, Parthun MR, Freitas MA (2013) H1 histones: current perspectives and challenges. Nucleic Acids Res 41(21):9593–9609

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hasson D, Panchenko T, Salimian KJ, Salman MU, Sekulic N, Alonso A, Warburton PE, Black BE (2013) The octamer is the major form of CENP-A nucleosomes at human centromeres. Nat Struct Mol Biol 20(6):687–695

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hayakawa K, Ohgane J, Tanaka S, Yagi S, Shiota K (2012) Oocyte-specific linker histone H1foo is an epigenomic modulator that decondenses chromatin and impairs pluripotency. Epigenetics 9:1029–1036

    Google Scholar 

  • Hendzel MJ, Lever MA, Crawford E, Th’ng JP (2004) The C-terminal domain is the primary determinant of histone H1 binding to chromatin in vivo. J Biol Chem 279(19):20028–20034

    CAS  PubMed  Google Scholar 

  • Henikoff S, Ahmad K, Malik HS (2001) The centromere paradox: Stable inheritance with rapidly evolving DNA. Science 293:1098–1102

    CAS  PubMed  Google Scholar 

  • Heo K, Kim H, Choi SH, Choi J, Kim K, Gu J, Lieber MR, Yang AS, An W (2008) FACT-mediated exchange of histone variant H2AX regulated by phosphorylation of H2AX and ADP-ribosylation of Spt16. Mol Cell 30(1):86–97

    CAS  PubMed  Google Scholar 

  • Hill DA (2001) Influence of linker histone H1 on chromatin remodeling. Biochem Cell Biol 79:317–324

    CAS  PubMed  Google Scholar 

  • Hu Y, Chopra V, Chopra R, Locascio JJ, Liao Z, Ding H, Zheng B, Matson WR, Ferrante RJ, Rosas HD, Hersch SM, Scherzer CR (2011) Transcriptional modulator H2A histone family, member Y (H2AFY) marks Huntington disease activity in man and mouse. Proc Natl Acad Sci USA 108(41):17141–17146

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ivashkevich A, Redon CE, Nakamura AJ, Martin RF, Martin OA (2012) Use of the γ-H2AX assay to monitor DNA damage and repair in translational cancer research. Cancer Lett 327(1–2):123–133

    CAS  PubMed Central  PubMed  Google Scholar 

  • Izzo A, Kamieniarz-Gdula K, Ramírez F, Noureen N, Kind J, Manke T, van Steensel B, Schneider R (2013) The genomic landscape of the somatic linker histone subtypes H1.1 to H1.5 in human cells. Cell Rep 3(6):2142–2154

    CAS  PubMed  Google Scholar 

  • Izzo A, Kamieniarz K, Schneider R (2008) The histone H1 family: specific members, specific functions? Biol Chem 389(4):333–343

    CAS  PubMed  Google Scholar 

  • Jansen LET, Black BE, Foltz DR, Cleveland DW (2007) Propagation of centromeric chromatin requires exit from mitosis. J Cell Biol 176:795–805

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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(8):941–945

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kamieniarz K, Izzo A, Dundr M, Tropberger P, Ozretic L, Kirfel J, Scheer E, Tropel P, Wisniewski JR, Tora L, Viville S, Buettner R, Schneider R (2012) A dual role of linker histone H1.4 Lys 34 acetylation in transcriptional activation. Genes Dev 26(8):797–802

    CAS  PubMed Central  PubMed  Google Scholar 

  • Keogh MC, Kim JA, Downey M, Fillingham J, Chowdhury D, Harrison JC, Onishi M, Datta N, Galicia S, Emili A, Lieberman J, Shen X, Buratowski S, Haber JE, Durocher D, Greenblatt JF, Krogan NJ (2006) A phosphatase complex that dephosphorylates gammaH2AX regulates DNA damage checkpoint recovery. Nature 439:497–501

    CAS  PubMed  Google Scholar 

  • Kouzarides T (2007) Chromatin modifications and their function. Cell 128(4):693–705

    CAS  PubMed  Google Scholar 

  • Lewis PW, Elsaesser SJ, Noh KM, 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(32):14075–14080

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lewis PW, Müller MM, Koletsky MS, Cordero F, Lin S, Banaszynski LA, Garcia BA, Muir TW, Becher OJ, Allis CD (2013) Inhibition of PRC2 activity by a gain-of-function H3 mutation found in pediatric glioblastoma. Science 340(6134):857–861

    CAS  PubMed Central  PubMed  Google Scholar 

  • Li A, Yu Y, Lee SC, Ishibashi T, Lees-Miller SP, Ausió J (2010) Phosphorylation of histone H2A.X by DNA-dependent protein kinase is not affected by core histone acetylation, but it alters nucleosome stability and histone H1 binding. J Biol Chem 285(23):17778–17788

    CAS  PubMed Central  PubMed  Google Scholar 

  • Li H, Kaminski MS, Li Y, Yildiz M, Ouillette P, Jones S, Fox H, Jacobi K, Saiya-Cork K, Bixby D, Lebovic D, Roulston D, Shedden K, Sabel M, Marentette L, Cimmino V, Chang AE, Malek SN. (2014) Mutations in linker histone genes HIST1H1 B, C, D and E, OCT2 (POU2F2), IRF8 and ARID1A underlying the pathogenesis of follicular lymphoma. Blood. [Epub ahead of print]

  • Li Z, Gadue P, Chen K, Jiao Y, Tuteja G, Schug J, Li W, Kaestner KH (2012) Foxa2 and H2A.Z mediate nucleosome depletion during embryonic stem cell differentiation. Cell 151(7):1608–1616

    CAS  PubMed Central  PubMed  Google Scholar 

  • Liu X, Li B, Gorovsky MA (1996) Essential and nonessential histone H2A variants in Tetrahymena thermophila. Mol Cell Biol 16:4305–4311

    CAS  PubMed Central  PubMed  Google Scholar 

  • Luger K, Mäder AW, Richmond RK, Sargent DF, Richmond TJ (1997) Crystal structure of the nucleosome core particle at 2.8 A resolution. Nature 389(6648):251–260

    CAS  PubMed  Google Scholar 

  • 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 143:725–736

    CAS  PubMed  Google Scholar 

  • Malik HS, Henikoff S (2003) Phylogenomics of the nucleosome. Nat Struct Biol 10:882–891

    CAS  PubMed  Google Scholar 

  • Martianov I, Brancorsini S, Catena R, Gansmuller A, Kotaja N, Parvinen M, Sassone-Corsi P, Davidson I (2005) Polar nuclear localization of H1T2, a histone H1 variant, required for spermatid elongation and DNA condensation during spermiogenesis. Proc Natl Acad Sci USA 102(8):2808–2813

    CAS  PubMed Central  PubMed  Google Scholar 

  • Marzluff WF, Gongidi P, Woods KR, Jin J, Maltais LJ (2002) The human and mouse replication-dependent histone genes. Genomics 80(5):487–498

    CAS  PubMed  Google Scholar 

  • Meneghini MD, Wu M, Madhani HD (2003) Conserved histone variant H2A.Z protects euchromatin from the ectopic spread of silent heterochromatin. Cell 112:e725–e736

    Google Scholar 

  • Miell MD, Fuller CJ, Guse A, Barysz HM, Downes A, Owen-Hughes T, Rappsilber J, Straight AF, Allshire RC (2013) CENP-A confers a reduction in height on octameric nucleosomes. Nat Struct Mol Biol 20(6):763–765

    CAS  PubMed Central  PubMed  Google Scholar 

  • Misteli T, Gunjan A, Hock R, Bustin M, Brown DT (2000) Dynamic binding of histone H1 to chromatin in living cells. Nature 408:877–881

    CAS  PubMed  Google Scholar 

  • Mito Y, Henikoff JG, Henikoff S (2005) Genome-scale profiling of histone H3.3 replacement patterns. Nat Genet 37:1090–1097

    CAS  PubMed  Google Scholar 

  • Mizusawa Y, Kuji N, Tanaka Y, Tanaka M, Ikeda E, Komatsu S, Kato S, Yoshimura Y (2010) Expression of human oocyte-specific linker histone protein and its incorporation into sperm chromatin during fertilization. Fertil Steril 93(4):1134–1141

    CAS  PubMed  Google Scholar 

  • Muthurajan UM, McBryant SJ, Lu X, Hansen JC, Luger K (2011) The linker region of macroH2A promotes self-association of nucleosomal arrays. J Biol Chem 286:23852–23864

    CAS  PubMed Central  PubMed  Google Scholar 

  • Nekrasov M, Amrichova J, Parker BJ, Soboleva TA, Jack C, Williams R, Huttley GA, Tremethick DJ (2012) Histone H2A.Z inheritance during the cell cycle and its impact on promoter organization and dynamics. Nat Struct Mol Biol 19:e1076–e1083

    Google Scholar 

  • 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 10:102–109

    CAS  PubMed  Google Scholar 

  • Padeganeh A, Ryan J, Boisvert J, Ladouceur AM, Dorn JF, Maddox PS (2013) Octameric CENP-A nucleosomes are present at human centromeres throughout the cell cycle. Curr Biol 23(9):764–769

    CAS  PubMed  Google Scholar 

  • Pandey NB, Chodchoy N, Liu TJ, Marzluff WF (1990) Introns in histone genes alter the distribution of 3 ends. Nucleic Acids Res 18:3161–3170

    CAS  PubMed Central  PubMed  Google Scholar 

  • Papamichos-Chronakis M, Krebs JE, Peterson CL (2006) Interplay between Ino80 and Swr1 chromatin remodeling enzymes regulates cell cycle checkpoint adaptation in response to DNA damage. Genes Dev 20:2437–2449

    CAS  PubMed Central  PubMed  Google Scholar 

  • Papamichos-Chronakis M, Watanabe S, Rando OJ, Peterson CL (2011) Global regulation of H2A.Z localization by the INO80 chromatinremodeling enzyme is essential for genome integrity. Cell 144:200–213

    CAS  PubMed Central  PubMed  Google Scholar 

  • Pasque V, Gillich A, Garrett N, Gurdon JB (2011) Histone variant macroH2A confers resistance to nuclear reprogramming. EMBO J 30(12):2373–2387

    CAS  PubMed Central  PubMed  Google Scholar 

  • Pérez-Montero S, Carbonell A, Morán T, Vaquero A, Azorín F (2013) The embryonic linker histone H1 variant of Drosophila, dBigH1, regulates zygotic genome activation. Dev Cell 26(6):578–590

    PubMed  Google Scholar 

  • Qiu JJ, Guo JJ, Lv TJ, Jin HY, Ding JX, Feng WW, Zhang Y, Hua KQ (2013) Prognostic value of centromere protein-A expression in patients with epithelial ovarian cancer. Tumour Biol 34(5):2971–2975

    CAS  PubMed  Google Scholar 

  • Rappa F, Greco A, Podrini C, Cappello F, Foti M, Bourgoin L, Peyrou M, Marino A, Scibetta N, Williams R, Mazzoccoli G, Federici M, Pazienza V, Vinciguerra M (2013) Immunopositivity for histone macroH2A1 isoforms marks steatosis-associated hepatocellular carcinoma. PLoS ONE 8(1):e54458

    CAS  PubMed Central  PubMed  Google Scholar 

  • Rasmussen TP, Huang T, Mastrangelo MA, Loring J, Panning B, Jaenisch R (1999) Messenger RNAs encoding mouse histone macroH2A1 isoforms are expressed at similar levels in male and female cells and result from alternative splicing. Nucleic Acids Res 27(18):3685–3689

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ratnakumar K, Duarte LF, LeRoy G, Hasson D, Smeets D, Vardabasso C, Bonisch C, Zeng T, Xiang B, Zhang DY, Li H, Wang X, Hake SB, Schermelleh L, Garcia BA, Bernstein E (2012) ATRX-mediated chromatin association of histone variant macroH2A1 regulates alpha-globin expression. Genes Dev 26:433–438

    CAS  PubMed Central  PubMed  Google Scholar 

  • Robinson PJ, Rhodes D (2006) Structure of the ‘30 nm’ chromatin fibre: a key role for the linker histone. Curr Opin Struct Biol 16:e336–e343

    Google Scholar 

  • Rogakou EP, Pilch DR, Orr AH, Ivanova VS, Bonner WM (1998) DNA doublestranded breaks induce histone H2AX phosphorylation on serine 139. J Biol Chem 273:5858–5868

    CAS  PubMed  Google Scholar 

  • Rogakou EP, Boon C, Redon C, Bonner WM (1999) Megabase chromatin domains involved in DNA double-strand breaks in vivo. J Cell Biol 146:905–916

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sancho M, Diani E, Beato M, Jordan A (2008) Depletion of human histone H1 variants uncovers specific roles in gene expression and cell growth. PLoS Genet 4(10):e1000227

    PubMed Central  PubMed  Google Scholar 

  • Sato S, Takahashi S, Asamoto M, Nakanishi M, Wakita T, Ogura Y, Yatabe Y, Shirai T (2012) Histone H1 expression in human prostate cancer tissues and cell lines. Pathol Int 62(2):84–92

    CAS  PubMed  Google Scholar 

  • Schwartz BE, Ahmad K (2005) Transcriptional activation triggers deposition and removal of the histone variant H3.3. Genes Dev 19(7):804–814

    CAS  PubMed Central  PubMed  Google Scholar 

  • Schwartzentruber J, Korshunov A, Liu XY, Jones DT, Pfaff E et al (2012) Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature 482(7384):226–231

    CAS  PubMed  Google Scholar 

  • Singh N, Basnet H, Wiltshire TD, Mohammad DH, Thompson JR, Héroux A, Botuyan MV, Yaffe MB, Couch FJ, Rosenfeld MG, Mer G (2012) Dual recognition of phosphoserine and phosphotyrosine in histone variant H2A.X by DNA damage response protein MCPH1. Proc Natl Acad Sci USA 109(36):14381–14386

    CAS  PubMed Central  PubMed  Google Scholar 

  • Skene PJ, Henikoff S (2013) Histone variants in pluripotency and disease. Development 140(12):2513–2524

    CAS  PubMed  Google Scholar 

  • 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(38):3423–3428

    CAS  PubMed  Google Scholar 

  • Stoldt S, Wenzel D, Schulze E, Doenecke D, Happel N (2007) G1 phase-dependent nucleolar accumulation of human histone H1x. Biol Cell 99(10):541–552

    CAS  PubMed  Google Scholar 

  • Strahl BD, Allis CD (2000) The language of covalent histone modifications. Nature 403(6765):41–45

    CAS  PubMed  Google Scholar 

  • 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 7:1121–1124

    CAS  PubMed  Google Scholar 

  • 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(1):51–61

    CAS  PubMed  Google Scholar 

  • Tanaka H, Iguchi N, Isotani A, Kitamura K, Toyama Y, Matsuoka Y, Onishi M, Masai K, Maekawa M, Toshimori K, Okabe M, Nishimune Y (2005) HANP1/H1T2, a novel histone H1-like protein involved in nuclear formation and sperm fertility. Mol Cell Biol 25(16):7107–7119

    CAS  PubMed Central  PubMed  Google Scholar 

  • Terme JM, Sesé B, Millán-Ariño L, Mayor R, Izpisúa Belmonte JC, Barrero MJ, Jordan A (2011) Histone H1 variants are differentially expressed and incorporated into chromatin during differentiation and reprogramming to pluripotency. J Biol Chem 286(41):35347–35357

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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(46):10852–10857

    CAS  PubMed  Google Scholar 

  • Th’ng JPH, Sung R, Ye M, Hendzel MJ (2005) H1 family histones in the nucleus. Control of binding and localization by the C-terminal domain. J Biol Chem 280:27809–27814

    PubMed  Google Scholar 

  • Till S, Ladurner AG (2009) Sensing NAD metabolites through macro domains. Front Biosci 14:3246–3258

    CAS  Google Scholar 

  • Turner BM (1993) Decoding the nucleosome. Cell 75(1):5–8

    CAS  PubMed  Google Scholar 

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

    PubMed Central  PubMed  Google Scholar 

  • van Daal A, Elgin SCR (1992) A histone variant, H2AvD, is essential in Drosophila melanogaster. Mol Biol Cell 3:593–602

    PubMed Central  PubMed  Google Scholar 

  • Voullaire LE, Slater HR, Petrovic V, Choo KH (1993) A functional marker centromere with no detectable alpha-satellite, satellite III, or CENP-B protein: activation of a latent centromere? Am J Hum Genet 52(6):1153–1163

    CAS  PubMed Central  PubMed  Google Scholar 

  • Walkiewicz MP, Dimitriadis EK, Dalal Y (2014) CENP-A octamers do not confer a reduction in nucleosome height by AFM. Nat Struct Mol Biol 21(1):2–3

    CAS  PubMed  Google Scholar 

  • Waterhouse AM, Procter JB, Martin DM, Clamp M, Barton GJ (2009) Jalview Version 2 – a multiple sequence alignment editor and analysis workbench. Bioinformatics 25:1189–1191

  • Xiao A, Li H, Shechter D, Ahn SH, Fabrizio LA, Erdjument-Bromage H, Ishibe-Murakami S, Wang B, Tempst P, Hofmann K, Patel DJ, Elledge SJ, Allis CD (2009) WSTF regulates the H2A.X DNA damage response via a novel tyrosine kinase activity. Nature 457:57–62

    CAS  PubMed Central  PubMed  Google Scholar 

  • Xu Y, Ayrapetov MK, Xu C, Gursoy-Yuzugullu O, Hu Y, Price BD (2012) Histone H2A.Z controls a critical chromatin remodeling step required for DNA double-strand break repair. Mol Cell 48(5):723–733

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yan W, Ma L, Burns KH, Matzuk MM (2003) HILS1 is a spermatid-specific linker histone H1-like protein implicated in chromatin remodeling during mammalian spermiogenesis. Proc Natl Acad Sci USA 100(18):10546–10551

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yang JW, Pendon C, Yang J, Haywood N, Chand A, Brown WR (2000) Human mini-chromosomes with minimal centromeres. Hum Mol Genet 9:1891–1902

    CAS  PubMed  Google Scholar 

  • Yoda K, Ando S, Morishita S, Houmura K, Hashimoto K, Takeyasu K, Okazaki T (2000) Human centromere protein A (CENP-A) can replace histone H3 in nucleosome reconstitution in vitro. Proc Natl Acad Sci USA 97:7266–7271

    CAS  PubMed Central  PubMed  Google Scholar 

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

    CAS  PubMed Central  PubMed  Google Scholar 

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Acknowledgements

We thank Poonam Bheda for critical reading of the manuscript and Adam Fiseha Kebede for helpful discussions. Work in the RS laboratory is supported by the Fondation pour la Recherche Médicale, the Agence Nationale de Recherche (ANR), INSERM, La Ligue National Contre La Cancer (Equipe Labellise) and an ERC starting grant.

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Biterge, B., Schneider, R. Histone variants: key players of chromatin. Cell Tissue Res 356, 457–466 (2014). https://doi.org/10.1007/s00441-014-1862-4

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