The Epigenetic Basis for Centromere Identity

  • Tanya Panchenko
  • Ben  E. BlackEmail author
Part of the Progress in Molecular and Subcellular Biology book series (PMSB, volume 48)


The centromere serves as the control locus for chromosome segregation at mitosis and meiosis. In most eukaryotes, including mammals, the location of the centromere is epigenetically defined. The contribution of both genetic and epigenetic determinants to centromere function is the subject of current investigation in diverse eukaryotes. Here we highlight key findings from several organisms that have shaped the current view of centromeres, with special attention to experiments that have elucidated the epigenetic nature of their specification. Recent insights into the histone H3 variant, CENP-A, which assembles into centromeric nucleosomes that serve as the epigenetic mark to perpetuate centromere identity, have added important mechanistic understanding of how centromere identity is initially established and subsequently maintained in every cell cycle.


Dicentric Chromosome Pericentromeric Heterochromatin Centromere Function Human Artificial Chromosome Centromeric Chromatin 
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.



Work in the Black Laboratory is supported by a Career Award in the Biomedical Sciences from the Burroughs Wellcome Fund and a grant (GM82989) from the NIH.


  1. Ahmad K, Henikoff S (2002) The histone variant H3.3 marks active chromatin by replication-independent nucleosome assembly. Mol Cell 9:1191–1200PubMedCrossRefGoogle Scholar
  2. Allshire RC, Javerzat JP, Redhead NJ, Cranston G (1994) Position effect variegation at fission yeast centromeres. Cell 76:157–169PubMedCrossRefGoogle Scholar
  3. Allshire RC, Nimmo ER, Ekwall K, Javerzat JP, Cranston G (1995) Mutations derepressing silent centromeric domains in fission yeast disrupt chromosome segregation. Genes Dev 9:218–233PubMedCrossRefGoogle Scholar
  4. Alonso A, Mahmood R, Li S, Cheung F, Yoda K, Warburton PE (2003) Genomic microarray analysis reveals distinct locations for the CENP-A binding domains in three human chromosome 13q32 neocentromeres. Hum Mol Genet 12:2711–2721PubMedCrossRefGoogle Scholar
  5. Amor DJ, Bentley K, Ryan J, Perry J, Wong L, Slater H, Choo KH (2004) Human centromere repositioning “in progress”. Proc Natl Acad Sci USA 101:6542–6547PubMedCrossRefGoogle Scholar
  6. Ananiev EV, Phillips RL, Rines HW (1998a) Chromosome-specific molecular organization of maize (Zea mays L.) centromeric regions. Proc Natl Acad Sci USA 95:13073–13078CrossRefGoogle Scholar
  7. Ananiev EV, Phillips RL, Rines HW (1998b) A knob-associated tandem repeat in maize capable of forming fold-back DNA segments: are chromosome knobs megatransposons. Proc Natl Acad Sci USA 95:10785–10790CrossRefGoogle Scholar
  8. Baker RE, Fitzgerald-Hayes M, O’Brien TC (1989) Purification of the yeast centromere binding protein CP1 and a mutational analysis of its binding site. J Biol Chem 264:10843–10850PubMedGoogle Scholar
  9. Barry AE, Howman EV, Cancilla MR, Saffery R, Choo KH (1999) Sequence analysis of an 80 kb human neocentromere. Hum Mol Genet 8:217–227PubMedCrossRefGoogle Scholar
  10. Barry AE, Bateman M, Howman EV, Cancilla MR, Tainton KM, Irvine DV, Saffery R, Choo KH (2000) The 10q25 neocentromere and its inactive progenitor have identical primary nucleotide sequence: further evidence for epigenetic modification. Genome Res 10:832–838PubMedCrossRefGoogle Scholar
  11. Black BE, Bassett EA (2008) The histone variant CENP-A and centromere specification. Curr Opin Cell Biol 20:91–100PubMedCrossRefGoogle Scholar
  12. Black BE, Foltz DR, Chakravarthy S, Luger K, Woods VL Jr, Cleveland DW (2004) Structural determinants for generating centromeric chromatin. Nature 430:578–582PubMedCrossRefGoogle Scholar
  13. Black BE, Brock MA, Bedard S, Woods VL Jr, Cleveland DW (2007a) An epigenetic mark generated by the incorporation of CENP-A into centromeric nucleosomes. Proc Natl Acad Sci USA 104:5008–5013CrossRefGoogle Scholar
  14. Black BE, Jansen LE, Maddox PS, Foltz DR, Desai AB, Shah JV, Cleveland DW (2007b) Centromere identity maintained by nucleosomes assembled with histone H3 containing the CENP-A targeting domain. Mol Cell 25:309–322CrossRefGoogle Scholar
  15. Bloom KS, Carbon J (1982) Yeast centromere DNA is in a unique and highly ordered structure in chromosomes and small circular minichromosomes. Cell 29:305–317PubMedCrossRefGoogle Scholar
  16. Blower MD, Karpen GH (2001) The role of Drosophila CID in kinetochore formation, cell-cycle progression and heterochromatin interactions. Nat Cell Biol 3:730–739PubMedCrossRefGoogle Scholar
  17. Blower MD, Sullivan BA, Karpen GH (2002) Conserved organization of centromeric chromatin in flies and humans. Dev Cell 2:319–330PubMedCrossRefGoogle Scholar
  18. Bram RJ, Kornberg RD (1987) Isolation of a Saccharomyces cerevisiae centromere DNA-binding protein, its human homolog, and its possible role as a transcription factor. Mol Cell Biol 7:403–409PubMedGoogle Scholar
  19. Bukvic N, Susca F, Gentile M, Tangari E, Ianniruberto A, Guanti G (1996) An unusual dicentric Y chromosome with a functional centromere with no detectable alpha-satellite. Hum Genet 97:453–456PubMedCrossRefGoogle Scholar
  20. Cai MJ, Davis RW (1989) Purification of a yeast centromere-binding protein that is able to distinguish single base-pair mutations in its recognition site. Mol Cell Biol 9:2544–2550PubMedGoogle Scholar
  21. Camahort R, Li B, Florens L, Swanson SK, Washburn MP, Gerton JL (2007) Scm3 is essential to recruit the histone h3 variant cse4 to centromeres and to maintain a functional kinetochore. Mol Cell 26:853–865PubMedCrossRefGoogle Scholar
  22. Carbon J, Clarke L (1984) Structural and functional analysis of a yeast centromere (CEN3). J Cell Sci Suppl 1:43–58PubMedGoogle Scholar
  23. Cardone MF, Alonso A, Pazienza M, Ventura M, Montemurro G, Carbone L, de Jong PJ, Stanyon R, D’Addabbo P, Archidiacono N, She X, Eichler EE, Warburton PE, Rocchi M (2006) Independent centromere formation in a capricious, gene-free domain of chromosome 13q21 in Old World monkeys and pigs. Genome Biol 7:R91PubMedCrossRefGoogle Scholar
  24. Carlson SR, Rudgers GW, Zieler H, Mach JM, Luo S, Grunden E, Krol C, Copenhaver GP, Preuss D (2007) Meiotic transmission of an in vitro-assembled autonomous maize minichromosome. PLoS Genet 3:1965–1974PubMedCrossRefGoogle Scholar
  25. Castillo AG, Mellone BG, Partridge JF, Richardson W, Hamilton GL, Allshire RC, Pidoux AL (2007) Plasticity of fission yeast CENP-A chromatin driven by relative levels of histone H3 and H4. PLoS Genet 3:e121PubMedCrossRefGoogle Scholar
  26. Chen ES, Saitoh S, Yanagida M, Takahashi K (2003) A cell cycle-regulated GATA factor promotes centromeric localization of CENP-A in fission yeast. Mol Cell 11:175–187PubMedCrossRefGoogle Scholar
  27. Chikashige Y, Kinoshita N, Nakaseko Y, Matsumoto T, Murakami S, Niwa O, Yanagida M (1989) Composite motifs and repeat symmetry in S. pombe centromeres: direct analysis by integration of NotI restriction sites. Cell 57:739–751PubMedCrossRefGoogle Scholar
  28. Chueh AC, Wong LH, Wong N, Choo KH (2005) Variable and hierarchical size distribution of L1-retroelement-enriched CENP-A clusters within a functional human neocentromere. Hum Mol Genet 14:85–93PubMedCrossRefGoogle Scholar
  29. Clarke L, Baum MP (1990) Functional analysis of a centromere from fission yeast: a role for centromere-specific repeated DNA sequences. Mol Cell Biol 10:1863–1872PubMedGoogle Scholar
  30. Clarke L, Carbon J (1980) Isolation of a yeast centromere and construction of functional small circular chromosomes. Nature 287:504–509PubMedCrossRefGoogle Scholar
  31. Clarke L, Carbon J (1983) Genomic substitutions of centromeres in Saccharomyces cerevisiae. Nature 305:23–28PubMedCrossRefGoogle Scholar
  32. Clarke L, Amstutz H, Fishel B, Carbon J (1986) Analysis of centromeric DNA in the fission yeast Schizosaccharomyces pombe. Proc Natl Acad Sci USA 83:8253–8257PubMedCrossRefGoogle Scholar
  33. Clarke L, Baum M, Marschall LG, Ngan VK, Steiner NC (1993) Structure and function of Schizosaccharomyces pombe centromeres. Cold Spring Harb Symp Quant Biol 58:687–695PubMedCrossRefGoogle Scholar
  34. Collins KA, Furuyama S, Biggins S (2004) Proteolysis contributes to the exclusive centromere localization of the yeast Cse4/CENP-A histone H3 variant. Curr Biol 14:1968–1972PubMedCrossRefGoogle Scholar
  35. Cottarel G, Shero JH, Hieter P, Hegemann JH (1989) A 125-base-pair CEN6 DNA fragment is sufficient for complete meiotic and mitotic centromere functions in Saccharomyces cerevisiae. Mol Cell Biol 9:3342–3349PubMedGoogle Scholar
  36. Cumberledge S, Carbon J (1987) Mutational analysis of meiotic and mitotic centromere function in Saccharomyces cerevisiae. Genetics 117:203–212PubMedGoogle Scholar
  37. Dalal Y, Wang H, Lindsay S, Henikoff S (2007) Tetrameric structure of centromeric nucleosomes in interphase Drosophila cells. PLoS Biol 5:e218PubMedCrossRefGoogle Scholar
  38. Dawe RK, Hiatt EN (2004) Plant neocentromeres: fast, focused, and driven. Chromosome Res 12:655–669PubMedCrossRefGoogle Scholar
  39. Dawe RK, Reed LM, Yu HG, Muszynski MG, Hiatt EN (1999) A maize homolog of mammalian CENPC is a constitutive component of the inner kinetochore. Plant Cell 11:1227–1238PubMedCrossRefGoogle Scholar
  40. Dennis ES, Peacock WJ (1984) Knob heterochromatin homology in maize and its relatives. J Mol Evol 20:341–350PubMedCrossRefGoogle Scholar
  41. du Sart D, Cancilla MR, Earle E, Mao JI, Saffery R, Tainton KM, Kalitsis P, Martyn J, Barry AE, Choo KH (1997) A functional neo-centromere formed through activation of a latent human centromere and consisting of non-alpha-satellite DNA. Nat Genet 16:144–153PubMedCrossRefGoogle Scholar
  42. Dunleavy EM, Pidoux AL, Monet M, Bonilla C, Richardson W, Hamilton GL, Ekwall K, McLaughlin PJ, Allshire RC (2007) A NASP (N1/N2)-related protein, Sim3, binds CENP-A and is required for its deposition at fission yeast centromeres. Mol Cell 28:1029–1044PubMedCrossRefGoogle Scholar
  43. Earnshaw W, Bordwell B, Marino C, Rothfield N (1986) Three human chromosomal autoantigens are recognized by sera from patients with anti-centromere antibodies. J Clin Invest 77: 426–430PubMedCrossRefGoogle Scholar
  44. Earnshaw WC, Cooke CA (1989) Proteins of the inner and outer centromere of mitotic chromosomes. Genome 31:541–552PubMedCrossRefGoogle Scholar
  45. Earnshaw WC, Rothfield N (1985) Identification of a family of human centromere proteins using autoimmune sera from patients with scleroderma. Chromosoma 91:313–321PubMedCrossRefGoogle Scholar
  46. Earnshaw WC, Sullivan KF, Machlin PS, Cooke CA, Kaiser DA, Pollard TD, Rothfield NF, Cleveland DW (1987) Molecular cloning of cDNA for CENP-B, the major human centromere autoantigen. J Cell Biol 104:817–829PubMedCrossRefGoogle Scholar
  47. Earnshaw WC, Ratrie H, 3rd, Stetten G (1989) Visualization of centromere proteins CENP-B and CENP-C on a stable dicentric chromosome in cytological spreads. Chromosoma 98:1–12PubMedCrossRefGoogle Scholar
  48. Ebersole TA, Ross A, Clark E, McGill N, Schindelhauer D, Cooke H, Grimes B (2000) Mammalian artificial chromosome formation from circular alphoid input DNA does not require telomere repeats. Hum Mol Genet 9:1623–1631PubMedCrossRefGoogle Scholar
  49. Eichler EE (1999) Repetitive conundrums of centromere structure and function. Hum Mol Genet 8:151–155PubMedCrossRefGoogle Scholar
  50. Ekwall K, Olsson T, Turner BM, Cranston G, Allshire RC (1997) Transient inhibition of histone deacetylation alters the structural and functional imprint at fission yeast centromeres. Cell 91:1021–1032PubMedCrossRefGoogle Scholar
  51. Fishel B, Amstutz H, Baum M, Carbon J, Clarke L (1988) Structural organization and functional analysis of centromeric DNA in the fission yeast Schizosaccharomyces pombe. Mol Cell Biol 8:754–763PubMedGoogle Scholar
  52. Fitzgerald-Hayes M (1987) Yeast centromeres. Yeast 3:187–200PubMedCrossRefGoogle Scholar
  53. Fitzgerald-Hayes M, Buhler JM, Cooper TG, Carbon J (1982a) Isolation and subcloning analysis of functional centromere DNA (CEN11) from Saccharomyces cerevisiae chromosome XI. Mol Cell Biol 2:82–87Google Scholar
  54. Fitzgerald-Hayes M, Clarke L, Carbon J (1982b) Nucleotide sequence comparisons and functional analysis of yeast centromere DNAs. Cell 29:235–244CrossRefGoogle Scholar
  55. Folco HD, Pidoux AL, Urano T, Allshire RC (2008) Heterochromatin and RNAi are required to establish CENP-A chromatin at centromeres. Science 319:94–97PubMedCrossRefGoogle Scholar
  56. Foltz DR, Jansen LE, Black BE, Bailey AO, Yates JR III, Cleveland DW (2006) The human CENP-A centromeric nucleosome-associated complex. Nat Cell Biol 8:458–469PubMedCrossRefGoogle Scholar
  57. Fujita Y, Hayashi T, Kiyomitsu T, Toyoda Y, Kokubu A, Obuse C, Yanagida M (2007) Priming of centromere for CENP-A recruitment by human hMis18alpha, hMis18beta, and M18BP1. Dev Cell 12:17–30PubMedCrossRefGoogle Scholar
  58. Funk M, Hegemann JH, Philippsen P (1989) Chromatin digestion with restriction endonucleases reveals 150-160 bp of protected DNA in the centromere of chromosome XIV in Saccharomyces cerevisiae. Mol Gen Genet 219:153–160PubMedCrossRefGoogle Scholar
  59. Furuyama S, Biggins S (2007) Centromere identity is specified by a single centromeric nucleosome in budding yeast. Proc Natl Acad Sci USA 104:14706–14711PubMedCrossRefGoogle Scholar
  60. Gaudet A, Fitzgerald-Hayes M (1987) Alterations in the adenine-plus-thymine-rich region of CEN3 affect centromere function in Saccharomyces cerevisiae. Mol Cell Biol 7:68–75PubMedGoogle Scholar
  61. Goh PY, Kilmartin JV (1993) NDC10: a gene involved in chromosome segregation in Saccharomyces cerevisiae. J Cell Biol 121:503–512PubMedCrossRefGoogle Scholar
  62. Grimes BR, Rhoades AA, Willard HF (2002) Alpha-satellite DNA and vector composition influence rates of human artificial chromosome formation. Mol Ther 5:798–805PubMedCrossRefGoogle Scholar
  63. Haaf T, Warburton PE, Willard HF (1992) Integration of human alpha-satellite DNA into simian chromosomes: centromere protein binding and disruption of normal chromosome segregation. Cell 70:681–696PubMedCrossRefGoogle Scholar
  64. Hahnenberger KM, Baum MP, Polizzi CM, Carbon J, Clarke L (1989) Construction of functional artificial minichromosomes in the fission yeast Schizosaccharomyces pombe. Proc Natl Acad Sci USA 86:577-581PubMedCrossRefGoogle Scholar
  65. Hahnenberger KM, Carbon J, Clarke L (1991) Identification of DNA regions required for mitotic and meiotic functions within the centromere of Schizosaccharomyces pombe chromosome I. Mol Cell Biol 11:2206–2215PubMedGoogle Scholar
  66. Hajra S, Ghosh SK, Jayaram M (2006) The centromere-specific histone variant Cse4p (CENP-A) is essential for functional chromatin architecture at the yeast 2-microm circle partitioning locus and promotes equal plasmid segregation. J Cell Biol 174:779–790PubMedCrossRefGoogle Scholar
  67. 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
  68. Hall AE, Keith KC, Hall SE, Copenhaver GP, Preuss D (2004) The rapidly evolving field of plant centromeres. Curr Opin Plant Biol 7:108–114PubMedCrossRefGoogle Scholar
  69. Hall IM, Shankaranarayana GD, Noma K, Ayoub N, Cohen A, Grewal SI (2002) Establishment and maintenance of a heterochromatin domain. Science 297:2232–2237PubMedCrossRefGoogle Scholar
  70. Han F, Lamb JC, Birchler JA (2006) High frequency of centromere inactivation resulting in stable dicentric chromosomes of maize. Proc Natl Acad Sci USA 103:3238–3243PubMedCrossRefGoogle Scholar
  71. Harrington JJ, Van Bokkelen G, Mays RW, Gustashaw K, Willard HF (1997) Formation of de novo centromeres and construction of first-generation human artificial microchromosomes. Nat Genet 15:345–355PubMedCrossRefGoogle Scholar
  72. Hayashi T, Fujita Y, Iwasaki O, Adachi Y, Takahashi K, Yanagida M (2004) Mis16 and Mis18 are required for CENP-A loading and histone deacetylation at centromeres. Cell 118:715–729PubMedCrossRefGoogle Scholar
  73. Hemmerich P, Weidtkamp-Peters S, Hoischen C, Schmiedeberg L, Erliandri I, Diekmann S (2008) Dynamics of inner kinetochore assembly and maintenance in living cells. J Cell Biol 180:1101–1114PubMedCrossRefGoogle Scholar
  74. Henikoff S, Ahmad K, Platero JS, van Steensel B (2000) Heterochromatic deposition of centromeric histone H3-like proteins. Proc Natl Acad Sci USA 97:716–721PubMedCrossRefGoogle Scholar
  75. Henning KA, Novotny EA, Compton ST, Guan XY, Liu PP, Ashlock MA (1999) Human artificial chromosomes generated by modification of a yeast artificial chromosome containing both human alpha satellite and single-copy DNA sequences. Proc Natl Acad Sci USA 96:592–597PubMedCrossRefGoogle Scholar
  76. Heun P, Erhardt S, Blower MD, Weiss S, Skora AD, Karpen GH (2006) Mislocalization of the Drosophila centromere-specific histone CID promotes formation of functional ectopic kinetochores. Dev Cell 10:303–315PubMedCrossRefGoogle Scholar
  77. Hiatt EN, Kentner EK, Dawe RK (2002) Independently regulated neocentromere activity of two classes of tandem repeat arrays. Plant Cell 14:407–420PubMedCrossRefGoogle Scholar
  78. Hieter P, Pridmore D, Hegemann JH, Thomas M, Davis RW, Philippsen P (1985) Functional selection and analysis of yeast centromeric DNA. Cell 42:913–921PubMedCrossRefGoogle Scholar
  79. Ikeno M, Grimes B, Okazaki T, Nakano M, Saitoh K, Hoshino H, McGill NI, Cooke H, Masumoto H (1998) Construction of YAC-based mammalian artificial chromosomes. Nat Biotechnol 16:431–439PubMedCrossRefGoogle Scholar
  80. Ishii K, Ogiyama Y, Chikashige Y, Soejima S, Masuda F, Kakuma T, Hiraoka Y, Takahashi K (2008) Heterochromatin integrity affects chromosome reorganization after centromere dysfunction. Science 321:1088–1091PubMedCrossRefGoogle Scholar
  81. Jansen LE, Black BE, Foltz DR, Cleveland DW (2007) Propagation of centromeric chromatin requires exit from mitosis. J Cell Biol 176:795–805PubMedCrossRefGoogle Scholar
  82. Jayaram M, Li YY, Broach JR (1983) The yeast plasmid 2mu circle encodes components required for its high copy propagation. Cell 34:95–104PubMedCrossRefGoogle Scholar
  83. Jayaram M, Sutton A, Broach JR (1985) Properties of REP3: a cis-acting locus required for stable propagation of the Saccharomyces cerevisiae plasmid 2 microns circle. Mol Cell Biol 5:2466–2475PubMedGoogle Scholar
  84. Jehn B, Niedenthal R, Hegemann JH (1991) In vivo analysis of the Saccharomyces cerevisiae centromere CDEIII sequence: requirements for mitotic chromosome segregation. Mol Cell Biol 11:5212–5221PubMedGoogle Scholar
  85. Jiang WD, Philippsen P (1989) Purification of a protein binding to the CDEI subregion of Saccharomyces cerevisiae centromere DNA. Mol Cell Biol 9:5585–5593PubMedGoogle Scholar
  86. Jin W, Melo JR, Nagaki K, Talbert PB, Henikoff S, Dawe RK, Jiang J (2004) Maize centromeres: organization and functional adaptation in the genetic background of oat. Plant Cell 16:571–581PubMedCrossRefGoogle Scholar
  87. Karpen GH, Spradling AC (1990) Reduced DNA polytenization of a minichromosome region undergoing position-effect variegation in Drosophila. Cell 63:97–107PubMedCrossRefGoogle Scholar
  88. Karpen GH, Spradling AC (1992) Analysis of subtelomeric heterochromatin in the Drosophila minichromosome Dp1187 by single P element insertional mutagenesis. Genetics 132:737–753PubMedGoogle Scholar
  89. Kato A, Lamb JC, Birchler JA (2004) Chromosome painting using repetitive DNA sequences as probes for somatic chromosome identification in maize. Proc Natl Acad Sci USA 101:13554–13559PubMedCrossRefGoogle Scholar
  90. Kikuchi Y (1983) Yeast plasmid requires a cis-acting locus and two plasmid proteins for its stable maintenance. Cell 35:487–493PubMedCrossRefGoogle Scholar
  91. Kuhn RM, Clarke L, Carbon J (1991) Clustered tRNA genes in Schizosaccharomyces pombe centromeric DNA sequence repeats. Proc Natl Acad Sci USA 88:1306–1310PubMedCrossRefGoogle Scholar
  92. Larin Z, Fricker MD, Tyler-Smith C (1994) De novo formation of several features of a centromere following introduction of a Y alphoid YAC into mammalian cells. Hum Mol Genet 3:689–695PubMedCrossRefGoogle Scholar
  93. Le MH, Duricka D, Karpen GH (1995) Islands of complex DNA are widespread in Drosophila centric heterochromatin. Genetics 141:283–303PubMedGoogle Scholar
  94. Lechner J, Carbon J (1991) A 240 kd multisubunit protein complex, CBF3, is a major component of the budding yeast centromere. Cell 64:717–725PubMedCrossRefGoogle Scholar
  95. Lo AW, Craig JM, Saffery R, Kalitsis P, Irvine DV, Earle E, Magliano DJ, Choo KH (2001a) A 330 kb CENP-A binding domain and altered replication timing at a human neocentromere. EMBO J 20:2087–2096CrossRefGoogle Scholar
  96. Lo AW, Magliano DJ, Sibson MC, Kalitsis P, Craig JM, Choo KH (2001b) A novel chromatin immunoprecipitation and array (CIA) analysis identifies a 460-kb CENP-A-binding neocentromere DNA. Genome Res 11:448–457CrossRefGoogle Scholar
  97. Maddox PS, Hyndman F, Monen J, Oegema K, Desai A (2007) Functional genomics identifies a Myb domain-containing protein family required for assembly of CENP-A chromatin. J Cell Biol 176:757–763PubMedCrossRefGoogle Scholar
  98. Maggert KA, Karpen GH (2001) The activation of a neocentromere in Drosophila requires proximity to an endogenous centromere. Genetics 158:1615–1628PubMedGoogle Scholar
  99. Maine GT, Surosky RT, Tye BK (1984) Isolation and characterization of the centromere from chromosome V (CEN5) of Saccharomyces cerevisiae. Mol Cell Biol 4:86–91PubMedGoogle Scholar
  100. Mann C, Davis RW (1986) Structure and sequence of the centromeric DNA of chromosome 4 in Saccharomyces cerevisiae. Mol Cell Biol 6:241–245PubMedGoogle Scholar
  101. Marshall OJ, Chueh AC, Wong LH, Choo KH (2008) Neocentromeres: new insights into centromere structure, disease development, and karyotype evolution. Am J Hum Genet 82:261–282PubMedCrossRefGoogle Scholar
  102. Masumoto H, Masukata H, Muro Y, Nozaki N, Okazaki T (1989) A human centromere antigen (CENP-B) interacts with a short specific sequence in alphoid DNA, a human centromeric satellite. J Cell Biol 109:1963–1973PubMedCrossRefGoogle Scholar
  103. Masumoto H, Ikeno M, Nakano M, Okazaki T, Grimes B, Cooke H, Suzuki N (1998) Assay of centromere function using a human artificial chromosome. Chromosoma 107:406–416PubMedCrossRefGoogle Scholar
  104. McClintock B (1939) The behavior in successive nuclear divisions of a chromosome broken at meiosis. Proc Natl Acad Sci USA 25:405–416PubMedCrossRefGoogle Scholar
  105. McClintock B (1941) The stability of broken ends of chromosomes in Zea mays. Genetics 26:234–282PubMedGoogle Scholar
  106. McGrew J, Diehl B, Fitzgerald-Hayes M (1986) Single base-pair mutations in centromere element III cause aberrant chromosome segregation in Saccharomyces cerevisiae. Mol Cell Biol 6:530–538PubMedGoogle Scholar
  107. Measday V, Hailey DW, Pot I, Givan SA, Hyland KM, Cagney G, Fields S, Davis TN, Hieter P (2002) Ctf3p, the Mis6 budding yeast homolog, interacts with Mcm22p and Mcm16p at the yeast outer kinetochore. Genes Dev 16:101–113PubMedCrossRefGoogle Scholar
  108. Meluh PB, Yang P, Glowczewski L, Koshland D, Smith MM (1998) Cse4p is a component of the core centromere of Saccharomyces cerevisiae. Cell 94:607–613PubMedCrossRefGoogle Scholar
  109. Mizuguchi G, Xiao H, Wisniewski J, Smith MM, Wu C (2007) Nonhistone Scm3 and histones CenH3-H4 assemble the core of centromere-specific nucleosomes. Cell 129:1153–1164PubMedCrossRefGoogle Scholar
  110. 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 7:1248–1255PubMedCrossRefGoogle Scholar
  111. Moreno-Moreno O, Torras-Llort M, Azorin F (2006) Proteolysis restricts localization of CID, the centromere-specific histone H3 variant of Drosophila, to centromeres. Nucleic Acids Res 34:6247–6255PubMedCrossRefGoogle Scholar
  112. Motamedi MR, Verdel A, Colmenares SU, Gerber SA, Gygi SP, Moazed D (2004) Two RNAi complexes, RITS and RDRC, physically interact and localize to noncoding centromeric RNAs. Cell 119:789–802PubMedCrossRefGoogle Scholar
  113. Mroczek RJ, Dawe RK (2003) Distribution of retroelements in centromeres and neocentromeres of maize. Genetics 165:809–819PubMedGoogle Scholar
  114. Mroczek RJ, Melo JR, Luce AC, Hiatt EN, Dawe RK (2006) The maize Ab10 meiotic drive system maps to supernumerary sequences in a large complex haplotype. Genetics 174:145–154PubMedCrossRefGoogle Scholar
  115. Murakami S, Matsumoto T, Niwa O, Yanagida M (1991) Structure of the fission yeast centromere cen3: direct analysis of the reiterated inverted region. Chromosoma 101:214–221PubMedCrossRefGoogle Scholar
  116. Murphy M, Fitzgerald-Hayes M (1990) Cis- and trans-acting factors involved in centromere function in Saccharomyces cerevisiae. Mol Microbiol 4:329–336PubMedCrossRefGoogle Scholar
  117. Murphy MR, Fowlkes DM, Fitzgerald-Hayes M (1991) Analysis of centromere function in Saccharomyces cerevisiae using synthetic centromere mutants. Chromosoma 101:189–197PubMedCrossRefGoogle Scholar
  118. Murphy TD, Karpen GH (1995) Localization of centromere function in a Drosophila minichromosome. Cell 82:599–609PubMedCrossRefGoogle Scholar
  119. Murzina NV, Pei XY, Zhang W, Sparkes M, Vicente-Garcia J, Pratap JV, McLaughlin SH, Ben-Shahar TR, Verreault A, Luisi BF, Laue ED (2008) Structural basis for the recognition of histone H4 by the histone-chaperone RbAp46. Structure 16:1077–1085PubMedCrossRefGoogle Scholar
  120. Nakano M, Cardinale S, Noskov VN, Gassmann R, Vagnarelli P, Kandels-Lewis S, Larionov V, Earnshaw WC, Masumoto H (2008) Inactivation of a human kinetochore by specific targeting of chromatin modifiers. Dev Cell 14:507–522PubMedCrossRefGoogle Scholar
  121. Nakaseko Y, Adachi Y, Funahashi S, Niwa O, Yanagida M (1986) Chromosome walking shows a highly homologous repetitive sequence present in all the centromere regions of fission yeast. EMBO J 5:1011–1021PubMedGoogle Scholar
  122. Nakayama J, Klar AJ, Grewal SI (2000) A chromodomain protein, Swi6, performs imprinting functions in fission yeast during mitosis and meiosis. Cell 101:307–317PubMedCrossRefGoogle Scholar
  123. Nakayama J, Rice JC, Strahl BD, Allis CD, Grewal SI (2001) Role of histone H3 lysine 9 methylation in epigenetic control of heterochromatin assembly. Science 292:110–113PubMedCrossRefGoogle Scholar
  124. Nasuda S, Hudakova S, Schubert I, Houben A, Endo TR (2005) Stable barley chromosomes without centromeric repeats. Proc Natl Acad Sci USA 102:9842–9847PubMedCrossRefGoogle Scholar
  125. Neitz M, Carbon J (1985) Identification and characterization of the centromere from chromosome XIV in Saccharomyces cerevisiae. Mol Cell Biol 5:2887–2893PubMedGoogle Scholar
  126. Neumann P, Yan H, Jiang J (2007) The centromeric retrotransposons of rice are transcribed and differentially processed by RNA interference. Genetics 176:749–761PubMedCrossRefGoogle Scholar
  127. Noma K, Allis CD, Grewal SI (2001) Transitions in distinct histone H3 methylation patterns at the heterochromatin domain boundaries. Science 293:1150–1155PubMedCrossRefGoogle Scholar
  128. Obuse C, Yang H, Nozaki N, Goto S, Okazaki T, Yoda K (2004) Proteomics analysis of the centromere complex from HeLa interphase cells: UV-damaged DNA binding protein 1 (DDB-1) is a component of the CEN-complex, while BMI-1 is transiently co-localized with the centromeric region in interphase. Genes Cells 9:105–120PubMedCrossRefGoogle Scholar
  129. Ohzeki J, Nakano M, Okada T, Masumoto H (2002) CENP-B box is required for de novo centromere chromatin assembly on human alphoid DNA. J Cell Biol 159:765–775PubMedCrossRefGoogle Scholar
  130. Okada M, Cheeseman IM, Hori T, Okawa K, McLeod IX, Yates JR III, Desai A, Fukagawa T (2006) The CENP-H-I complex is required for the efficient incorporation of newly synthesized CENP-A into centromeres. Nat Cell Biol 8:446–457PubMedCrossRefGoogle Scholar
  131. Okada T, Ohzeki J, Nakano M, Yoda K, Brinkley WR, Larionov V, Masumoto H (2007) CENP-B controls centromere formation depending on the chromatin context. Cell 131:1287–1300PubMedCrossRefGoogle Scholar
  132. Ortiz J, Stemmann O, Rank S, Lechner J (1999) A putative protein complex consisting of Ctf19, Mcm21, and Okp1 represents a missing link in the budding yeast kinetochore. Genes Dev 13:1140–1155PubMedCrossRefGoogle Scholar
  133. Palmer DK, O’Day K, Margolis RL (1989) Biochemical analysis of CENP-A, a centromeric protein with histone-like properties. Prog Clin Biol Res 318:61–72PubMedGoogle Scholar
  134. Palmer DK, O’Day K, Trong HL, Charbonneau H, Margolis RL (1991) Purification of the centromere-specific protein CENP-A and demonstration that it is a distinctive histone. Proc Natl Acad Sci USA 88:3734–3738PubMedCrossRefGoogle Scholar
  135. Palmer DK, O’Day K, Wener MH, Andrews BS, Margolis RL (1987) A 17-kD centromere protein (CENP-A) copurifies with nucleosome core particles and with histones. J Cell Biol 104:805–815PubMedCrossRefGoogle Scholar
  136. Panzeri L, Philippsen P (1982) Centromeric DNA from chromosome VI in Saccharomyces cerevisiae strains. EMBO J 1:1605–1611PubMedGoogle Scholar
  137. Partridge JF, Borgstrom B, Allshire RC (2000) Distinct protein interaction domains and protein spreading in a complex centromere. Genes Dev 14:783–791PubMedGoogle Scholar
  138. Peacock WJ, Dennis ES, Rhoades MM, Pryor AJ (1981) Highly repeated DNA sequence limited to knob heterochromatin in maize. Proc Natl Acad Sci USA 78:4490–4494PubMedCrossRefGoogle Scholar
  139. Pidoux AL, Richardson W, Allshire RC (2003) Sim4: a novel fission yeast kinetochore protein required for centromeric silencing and chromosome segregation. J Cell Biol 161:295–307PubMedCrossRefGoogle Scholar
  140. Polizzi C, Clarke L (1991) The chromatin structure of centromeres from fission yeast: differentiation of the central core that correlates with function. J Cell Biol 112:191–201PubMedCrossRefGoogle Scholar
  141. Ray-Gallet D, Quivy JP, Scamps C, Martini EM, Lipinski M, Almouzni G (2002) HIRA is critical for a nucleosome assembly pathway independent of DNA synthesis. Mol Cell 9:1091–1100PubMedCrossRefGoogle Scholar
  142. Rhoades MM, Vilkomerson H (1942) On the anaphase movement of chromosomes. Proc Natl Acad Sci USA 28:433–436PubMedCrossRefGoogle Scholar
  143. Rivera H, Vassquez AI, Ayala-Madrigal ML, Ramirez-Duenas ML, Davalos IP (1996) Alphoidless centromere of a familial unstable inverted Y chromosome. Ann Genet 39:236–239PubMedGoogle Scholar
  144. Saffery R, Irvine DV, Griffiths B, Kalitsis P, Wordeman L, Choo KH (2000) Human centromeres and neocentromeres show identical distribution patterns of >20 functionally important kinetochore-associated proteins. Hum Mol Genet 9:175–185PubMedCrossRefGoogle Scholar
  145. Saffery R, Wong LH, Irvine DV, Bateman MA, Griffiths B, Cutts SM, Cancilla MR, Cendron AC, Stafford AJ, Choo KH (2001) Construction of neocentromere-based human minichromosomes by telomere-associated chromosomal truncation. Proc Natl Acad Sci USA 98:5705–5710PubMedCrossRefGoogle Scholar
  146. Saitoh S, Takahashi K, Yanagida M (1997) Mis6, a fission yeast inner centromere protein, acts during G1/S and forms specialized chromatin required for equal segregation. Cell 90:131–143PubMedCrossRefGoogle Scholar
  147. Schueler MG, Sullivan BA (2006) Structural and functional dynamics of human centromeric chromatin. Annu Rev Genomics Hum Genet 7:301–313PubMedCrossRefGoogle Scholar
  148. Schueler MG, Higgins AW, Rudd MK, Gustashaw K, Willard HF (2001) Genomic and genetic definition of a functional human centromere. Science 294:109–115PubMedCrossRefGoogle Scholar
  149. Schuh M, Lehner CF, Heidmann S (2007) Incorporation of Drosophila CID/CENP-A and CENP-C into centromeres during early embryonic anaphase. Curr Biol 17:237–243PubMedCrossRefGoogle Scholar
  150. Scott-Drew S, Murray JA (1998) Localisation and interaction of the protein components of the yeast 2 mu circle plasmid partitioning system suggest a mechanism for plasmid inheritance. J Cell Sci 111(Pt 13):1779–1789PubMedGoogle Scholar
  151. Shelby RD, Monier K, Sullivan KF (2000) Chromatin assembly at kinetochores is uncoupled from DNA replication. J Cell Biol 151:1113–1118PubMedCrossRefGoogle Scholar
  152. 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 58:15–25PubMedCrossRefGoogle Scholar
  153. Som T, Armstrong KA, Volkert FC, Broach JR (1988) Autoregulation of 2 micron circle gene expression provides a model for maintenance of stable plasmid copy levels. Cell 52:27–37PubMedCrossRefGoogle Scholar
  154. Sorger PK, Severin FF, Hyman AA (1994) Factors required for the binding of reassembled yeast kinetochores to microtubules in vitro. J Cell Biol 127:995–1008PubMedCrossRefGoogle Scholar
  155. Steiner NC, Clarke L (1994) A novel epigenetic effect can alter centromere function in fission yeast. Cell 79:865–874PubMedCrossRefGoogle Scholar
  156. Steiner NC, Hahnenberger KM, Clarke L (1993) Centromeres of the fission yeast Schizosaccharomyces pombe are highly variable genetic loci. Mol Cell Biol 13:4578–4587PubMedGoogle Scholar
  157. Stinchcomb DT, Struhl K, Davis RW (1979) Isolation and characterisation of a yeast chromosomal replicator. Nature 282:39–43PubMedCrossRefGoogle Scholar
  158. Stinchcomb DT, Mann C, Davis RW (1982) Centromeric DNA from Saccharomyces cerevisiae. J Mol Biol 158:157–190PubMedCrossRefGoogle Scholar
  159. Stoler S, Keith KC, Curnick KE, Fitzgerald-Hayes M (1995) A mutation in CSE4, an essential gene encoding a novel chromatin-associated protein in yeast, causes chromosome nondisjunction and cell cycle arrest at mitosis. Genes Dev 9:573–586PubMedCrossRefGoogle Scholar
  160. Stoler S, Rogers K, Weitze S, Morey L, Fitzgerald-Hayes M, Baker RE (2007) Scm3, an essential Saccharomyces cerevisiae centromere protein required for G2/M progression and Cse4 localization. Proc Natl Acad Sci USA 104:10571–10576PubMedCrossRefGoogle Scholar
  161. Sugata N, Li S, Earnshaw WC, Yen TJ, Yoda K, Masumoto H, Munekata E, Warburton PE, Todokoro K (2000) Human CENP-H multimers colocalize with CENP-A and CENP-C at active centromere--kinetochore complexes. Hum Mol Genet 9:2919–2926PubMedCrossRefGoogle Scholar
  162. Sullivan BA, Karpen GH (2004) Centromeric chromatin exhibits a histone modification pattern that is distinct from both euchromatin and heterochromatin. Nat Struct Mol Biol 11:1076–1083PubMedCrossRefGoogle Scholar
  163. Sullivan BA, Schwartz S (1995) Identification of centromeric antigens in dicentric Robertsonian translocations: CENP-C and CENP-E are necessary components of functional centromeres. Hum Mol Genet 4:2189–2197PubMedCrossRefGoogle Scholar
  164. Sullivan BA, Willard HF (1998) Stable dicentric X chromosomes with two functional centromeres. Nat Genet 20:227–228PubMedCrossRefGoogle Scholar
  165. 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 127:581–592PubMedCrossRefGoogle Scholar
  166. Sun X, Wahlstrom J, Karpen G (1997) Molecular structure of a functional Drosophila centromere. Cell 91:1007–1019PubMedCrossRefGoogle Scholar
  167. Sun X, Le HD, Wahlstrom JM, Karpen GH (2003) Sequence analysis of a functional Drosophila centromere. Genome Res 13:182–194PubMedCrossRefGoogle Scholar
  168. 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
  169. Takahashi K, Murakami S, Chikashige Y, Funabiki H, Niwa O, Yanagida M (1992) A low copy number central sequence with strict symmetry and unusual chromatin structure in fission yeast centromere. Mol Biol Cell 3:819–835PubMedGoogle Scholar
  170. Takahashi K, Chen ES, Yanagida M (2000) Requirement of Mis6 centromere connector for localizing a CENP-A-like protein in fission yeast. Science 288:2215–2219PubMedCrossRefGoogle Scholar
  171. Takayama Y, Sato H, Saitoh S, Ogiyama Y, Masuda F, Takahashi K (2008) Biphasic incorporation of centromeric histone CENP-A in fission yeast. Mol Biol Cell 19:682–690PubMedCrossRefGoogle Scholar
  172. Topp CN, Zhong CX, Dawe RK (2004) Centromere-encoded RNAs are integral components of the maize kinetochore. Proc Natl Acad Sci USA 101:15986–15991PubMedCrossRefGoogle Scholar
  173. Tower J, Karpen GH, Craig N, Spradling AC (1993) Preferential transposition of Drosophila P elements to nearby chromosomal sites. Genetics 133:347–359PubMedGoogle Scholar
  174. Tyler-Smith C, Gimelli G, Giglio S, Floridia G, Pandya A, Terzoli G, Warburton PE, Earnshaw WC, Zuffardi O (1999) Transmission of a fully functional human neocentromere through three generations. Am J Hum Genet 64:1440–1444PubMedCrossRefGoogle Scholar
  175. Valdivia MM, Brinkley BR (1985) Fractionation and initial characterization of the kinetochore from mammalian metaphase chromosomes. J Cell Biol 101:1124–1134PubMedCrossRefGoogle Scholar
  176. Ventura M, Weigl S, Carbone L, Cardone MF, Misceo D, Teti M, D’Addabbo P, Wandall A, Bjorck E, de Jong PJ, She X, Eichler EE, Archidiacono N, Rocchi M (2004) Recurrent sites for new centromere seeding. Genome Res 14:1696–1703PubMedCrossRefGoogle Scholar
  177. Verdel A, Jia S, Gerber S, Sugiyama T, Gygi S, Grewal SI, Moazed D (2004) RNAi-mediated targeting of heterochromatin by the RITS complex. Science 303:672–676PubMedCrossRefGoogle Scholar
  178. Volpe TA, Kidner C, Hall IM, Teng G, Grewal SI, Martienssen RA (2002) Regulation of heterochromatic silencing and histone H3 lysine-9 methylation by RNAi. Science 297:1833–1837PubMedCrossRefGoogle Scholar
  179. 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 52:1153–1163PubMedGoogle Scholar
  180. Warburton PE, Cooke HJ (1997) Hamster chromosomes containing amplified human alpha-satellite DNA show delayed sister chromatid separation in the absence of de novo kinetochore formation. Chromosoma 106:149–159PubMedCrossRefGoogle Scholar
  181. Warburton PE, Cooke CA, Bourassa S, Vafa O, Sullivan BA, Stetten G, Gimelli G, Warburton D, Tyler-Smith C, Sullivan KF, Poirier GG, Earnshaw WC (1997) Immunolocalization of CENP-A suggests a distinct nucleosome structure at the inner kinetochore plate of active centromeres. Curr Biol 7:901–904PubMedCrossRefGoogle Scholar
  182. Warburton PE, Dolled M, Mahmood R, Alonso A, Li S, Naritomi K, Tohma T, Nagai T, Hasegawa T, Ohashi H, Govaerts LC, Eussen BH, Van Hemel JO, Lozzio C, Schwartz S, Dowhanick-Morrissette JJ, Spinner NB, Rivera H, Crolla JA, Yu C, Warburton D (2000) Molecular cytogenetic analysis of eight inversion duplications of human chromosome 13q that each contain a neocentromere. Am J Hum Genet 66:1794–1806PubMedCrossRefGoogle Scholar
  183. Westermann S, Cheeseman IM, Anderson S, Yates JR III, Drubin DG, Barnes G (2003) Architecture of the budding yeast kinetochore reveals a conserved molecular core. J Cell Biol 163:215–222PubMedCrossRefGoogle Scholar
  184. Willard HF (1991) Evolution of alpha satellite. Curr Opin Genet Dev 1:509–514PubMedCrossRefGoogle Scholar
  185. Williams BC, Murphy TD, Goldberg ML, Karpen GH (1998) Neocentromere activity of structurally acentric mini-chromosomes in Drosophila. Nat Genet 18:30–37PubMedCrossRefGoogle Scholar
  186. Worcel A, Han S, Wong ML (1978) Assembly of newly replicated chromatin. Cell 15:969–977PubMedCrossRefGoogle Scholar
  187. Wu RS, Tsai S, Bonner WM (1982) Patterns of histone variant synthesis can distinguish G0 from G1 cells. Cell 31:367–374PubMedCrossRefGoogle Scholar
  188. Yu HG, Hiatt EN, Chan A, Sweeney M, Dawe RK (1997) Neocentromere-mediated chromosome movement in maize. J Cell Biol 139:831–840PubMedCrossRefGoogle Scholar
  189. Zhang W, Lee HR, Koo DH, Jiang J (2008) Epigenetic modification of centromeric chromatin: hypomethylation of DNA sequences in the CENH3-associated chromatin in Arabidopsis thaliana and maize. Plant Cell 20:25–34PubMedCrossRefGoogle Scholar
  190. Zheng YZ, Roseman RR, Carlson WR (1999) Time course study of the chromosome-type breakage-fusion-bridge cycle in maize. Genetics 153:1435–1444PubMedGoogle Scholar
  191. Zhong CX, Marshall JB, Topp C, Mroczek R, Kato A, Nagaki K, Birchler JA, Jiang J, Dawe RK (2002) Centromeric retroelements and satellites interact with maize kinetochore protein CENH3. Plant Cell 14:2825–2836PubMedCrossRefGoogle Scholar
  192. Zinkowski RP, Meyne J, Brinkley BR (1991) The centromere-kinetochore complex: a repeat subunit model. J Cell Biol 113:1091–1110PubMedCrossRefGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  1. 1.Department of Biochemistry and BiophysicsUniversity of PennsylvaniaPA

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