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Centromere identity: a challenge to be faced

Molecular Genetics and Genomics volume 284, pages 75–94 (2010)Cite this article

Abstract

The centromere is a genetic locus, required for faithful chromosome segregation, where spindle fibers attach to the chromosome through kinetochore. Loss of centromere or formation of multiple centromeres on a single chromosome leads to chromosome missegregation or chromosome breakage, respectively, which are detrimental for fitness and survival of a cell. Therefore, understanding the mechanism of centromere locus determination on the chromosome and perpetuation of such a locus in subsequent generation (known as centromere identity) is very fundamental to combat conditions like aneuploidy, spontaneous abortion, developmental defects, cell lethality and cancer. Recent studies have come up with different models to explain centromere identity. However, the exact mechanism still remains elusive. It has been observed that most eukaryotic centromeres are determined epigenetically rather than by a DNA sequence. The epigenetic marks that are instrumental in determining centromere identity are the histone H3 variant, CENP-A and the specialized posttranslational modification of the core histones. Here we will review the recent studies on the factors responsible for generating unique centromeric chromatin and how it perpetuates during cell division giving the present-day models. We will further focus on the probable mechanism of de novo centromere formation with an example of neocentromere. As a matter of similitude, this review will include marking extrachromosomal chromatin to be served as a partitioning locus by deposition of CENP-A homolog in budding yeast.

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Abbreviations

CENP-A:

Centromeric protein A

CCAN:

Constitutive centromere-associated network

CHD1:

Chromodomain helicase DNA-binding protein 1

HJURP:

Holliday junction recognition protein

KNL2:

Kinetochore null phenotype

NURF:

Nucleosome remodeling factor

NASP:

Nuclear autoantigenic sperm protein

References

  • Agudo M, Abad JP, Molina I, Losada A, Ripoll P, Villasante A (2000) A dicentric chromosome of Drosophila melanogaster showing alternate centromere inactivation. Chromosoma 109(3):190–196

    Article  CAS  PubMed  Google Scholar 

  • Aguilera A (2005) mRNA processing and genomic instability. Nat Struct Mol Biol 12:737–738

    Article  CAS  PubMed  Google Scholar 

  • Allshire RC, Karpen GH (2008) Epigenetic regulation of centromeric chromatin: old dogs, new tricks? Nat Rev Genet 9(12):923–937

    Article  CAS  PubMed  Google Scholar 

  • Alonso A, Hasson D, Cheung F, Warburton PE (2010) A paucity of heterochromatin at functional human neocentromeres. Epigenetics Chromatin 3(1):6

    Article  PubMed  CAS  Google Scholar 

  • Barry AE, Howman EV, Cancilla MR, Saffery R, Choo KH (1999) Sequence analysis of an 80 kb human neocentromere. Hum Mol Genet 8(2):217–227

    Article  CAS  PubMed  Google Scholar 

  • Baum M, Sanyal K, Mishra PK, Thaler N, Carbon J (2006) Formation of functional centromeric chromatin is specified epigenetically in Candida albicans. Proc Natl Acad Sci USA 103(40):14877–14882

    Article  CAS  PubMed  Google Scholar 

  • Bernad R, Sánchez P, Losada A (2009) Epigenetic specification of centromeres by CENP-A. Exp Cell Res 315(19):3233–3241

    Article  CAS  PubMed  Google Scholar 

  • Black BE, Bassett EA (2008) The histone variant CENP-A and centromere specification. Curr Opin Cell Biol 20:91–100

    Article  CAS  PubMed  Google Scholar 

  • Black BE, Foltz DR, Chakravarthy S, Luger K, Woods VL Jr, Cleveland DW (2004) Structural determinants for generating centromeric chromatin. Nature 430:578–882

    Article  CAS  PubMed  Google Scholar 

  • 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(12):5008–5013

    Article  CAS  PubMed  Google Scholar 

  • 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 25:309–322

    Article  CAS  PubMed  Google Scholar 

  • Blower MD, Sullivan BA, Karpen GH (2002) Conserved organization of centromeric chromatin in flies and humans. Dev Cell 2:319–330

    Article  CAS  PubMed  Google Scholar 

  • Blower MD, Daigle T, Kaufman T, Karpen GH (2006) Drosophila CENP-A mutations cause a BubRa dependent early mitotic delay without normal localization of kinetochore components. PLoS Genet 2(7):e110

    Article  PubMed  CAS  Google Scholar 

  • Broach JR, Atkins JF, McGill C, Chow L (1979) Identification and mapping of the transcriptional and translational products of the yeast plasmid, 2 mu circle. Cell 16(4):827–839

    Article  CAS  PubMed  Google Scholar 

  • Buscaino A, Allshire R, Pidoux A (2010) Building centromeres: home sweet home or a nomadic existence? Curr Opin Genet Dev 20(2):118–126

    Article  CAS  PubMed  Google Scholar 

  • Camahort R, Shivaraju M, Mattingly M, Li B, Nakanishi S et al (2009) Cse4 is part of an octameric nucleosome in budding yeast. Mol Cell 35(6):794–805

    Article  CAS  PubMed  Google Scholar 

  • Carroll CW, Straight AF (2006) Centromere formation: from epigenetic to self-assembly. Trends in Cell Biol 16(2):70–77

    Article  CAS  Google Scholar 

  • Carroll CW, Silva MCC, Godek KM, Jansen LET, Straight AF (2009) Centromere assembly requires the direct recognition of CENP-A nucleosomes by CENP-N. Nat Cell Biol 11:896–902

    Article  CAS  PubMed  Google Scholar 

  • Cheeseman IM, Desai A (2008) Molecular architecture of the kinetochore-microtubule interface. Nat Rev Mol Cell Biol 9:33–46

    Article  CAS  PubMed  Google Scholar 

  • Chen Y, Baker RE, Keith KC, Harris K, Stoler S, Fitzgerald-Hayes M (2000) The N terminus of the centromere H3 like protein Cse4p performs an essential function distinct from that of the histone fold domain. Mol Cell Biol 20(18):7037–7048

    Article  CAS  PubMed  Google Scholar 

  • Chueh AC, Northrop EL, Brettingham-Moore KH, Choo KH, Wong LH (2009) LINE retrotransposone RNA is an essential structural and functional epigenetic component of a core neocentromeric chromatin. PLoS Genet 5(1):e1000354

    Article  PubMed  CAS  Google Scholar 

  • 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(21):1968–1972

    Article  CAS  PubMed  Google Scholar 

  • Cui H, Ghosh SK, Jayaram M (2009) The selfish yeast plasmid uses the nuclear motor Kip1p but not Cin8p for its localization and equal segregation. J Cell Biol 185(2):251–264

    Article  CAS  PubMed  Google Scholar 

  • Dai J, Sullivan BA, Higgins JM (2006) Regulation of mitotic chromosome cohesion by Haspin and Aurora B. Dev Cell 11:741–750

    Article  CAS  PubMed  Google Scholar 

  • Dalal Y (2009) Epigenetic specification of centromeres. Biochem Cell Biol 87:273–282

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Depinet TW, Zackowski JL, Earnshaw WC, Kaffe S, Sekhon GS et al (1997) Characterization of neo-centromeres in marker chromosomes lacking detactable alpha-satellite DNA. Hum Mol Genet 6(8):1195–1204

    Article  CAS  PubMed  Google Scholar 

  • du Sart D, Cancilla MR, Earle E, Mao J, Saffery R et al (1997) A functional neo-centromere formed through activation of a latent human centromere and consisting of non-alpha-satellite DNA. Nat Genet 16:144–153

    Article  CAS  PubMed  Google Scholar 

  • Du Y, Topp CN, Dawe RK (2010) DNA binding of centromere protein C (CENP-C) is stabilized by single stranded RNA. PLoS Genet 6(2):e1000835

    Article  PubMed  CAS  Google Scholar 

  • Dunleavy EM, Pidoux AL, Monet M, Bonilla C, Richardson W et al (2007) A NASP (N1/N2)-Related protein, Sim3, Binds CENP-A and is required for its deposition at fission yeast centromeres. Mol Cell 28:1029–1044

    Article  CAS  PubMed  Google Scholar 

  • Dunleavy EM, Roche D, Tagami H, Lacoste N, Ray-Gallet D et al (2009) HJURP is a cell-cycle-dependent maintenance and deposition factor of CENP-A at centromeres. Cell 137:485–497

    Article  CAS  PubMed  Google Scholar 

  • Earnshaw WC, Migeon BA (1985) Three related centromere proteins are absent from the inactive centromere of a stable isodicentric chromosome. Chromosoma (Berl) 92:290–296

    Article  CAS  Google Scholar 

  • Earnshaw WC, Ratrie H, Stetten G (1989) Visualization of centromere proteins CENP-B and CENP-C on a stable dicentric chromosome in cytological spreads. Chromosoma (Berl) 98:1–12

    Article  CAS  Google Scholar 

  • English CM, Maluf NK, Tripet B, Churchill ME, Tyler JK (2005) ASF1 binds to a heterodimer of histones H3 and H4: a two-step mechanism for the assembly of the H3–H4 heterotetramer on DNA. Biochemistry 44(42):13673–13682

    Article  CAS  PubMed  Google Scholar 

  • English CM, Adkins MW, Carson JJ, Churchill ME, Tyler JK (2006) Structural basis for the histone chaperone activity of Asf1. Cell 127(3):495–508

    Article  CAS  PubMed  Google Scholar 

  • Folco HD, Pidoux AL, Urano T, Allshire RC (2008) Heterochromatin and RNAi Are required to establish CENP-A chromatin at centromeres. Science 319:94–97

    Article  CAS  PubMed  Google Scholar 

  • Foltz DR, Jansen LE, Black BE, Bailey AO, Yates JR 3rd, Cleveland DW (2006) The human CENP-A centromeric nucleosome associated complex. Nat Cell Biol 8:458–469

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • 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 12:17–30

    Article  CAS  PubMed  Google Scholar 

  • Furuyama S, Biggins S (2007) Centromere identity is specified by a single centromeric nucleosome in budding yeast. Proc Natl Acad Sci USA 104:14706–14711

    Article  CAS  PubMed  Google Scholar 

  • Furuyama T, Henikoff S (2009) Centromeric nucleosomes induces positive DNA supercoils. Cell 138(1):104–113

    Article  CAS  PubMed  Google Scholar 

  • Furuyama T, Dalal Y, Henikoff S (2006) Chaperone-mediated assembly of centromeric chromatin in vitro. Proc Natl Acad Sci USA 103:6172–6177

    Article  CAS  PubMed  Google Scholar 

  • Gartenberg M (2009) Heterochromatin and the cohesion of sister chromatids. Chromosome Res 17(2):229–238

    Article  CAS  PubMed  Google Scholar 

  • Ghosh SK, Hajra S, Paek A, Jayaram M (2006) Mechanisms for chromosome and plasmid segregation. Ann Rev Biochem 75:211–241

    Article  CAS  PubMed  Google Scholar 

  • Ghosh SK, Hajra S, Jayaram M (2007) Faithful segregation of the multicopy yeast plasmid through cohesin mediated recognition of sisters. Proc Natl Acad Sci USA 104(32):13034–13039

    Article  CAS  PubMed  Google Scholar 

  • Ghosh SK, Huang CC, Hajra S, Jayaram M (2010) Yeast cohesin complex embraces 2 micron plasmid sisters in a tri-linked catenane complex. Nucleic Acids Res 38(2):570–584

    Article  CAS  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(2):525–530

    Article  CAS  PubMed  Google Scholar 

  • Greiner M, Caesar S, Schlenstedt G (2004) The histones H2A/H2B and H3/H4 are imported into yeast nucleus by different mechanisms. Eur J Cell Biol 83(10):511–520

    Article  CAS  PubMed  Google Scholar 

  • Groth A, Corpet A, Cook AJ, Roche D, Bartek J, Lukas J, Almouzni G (2007) Regulation of replication fork progression through histone supply and demand. Science 318(5858):1928–1931

    Article  CAS  PubMed  Google Scholar 

  • Grünweller A, Ehrenhofer-Murray AE (2002) A novel yeast silencer. the 2mu origin of Saccharomyces cerevisiae has HST3-, MIG1- and SIR-dependent silencing activity. Genetics 162(1):59–71

    PubMed  Google Scholar 

  • 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(6):779–790

    Article  CAS  PubMed  Google Scholar 

  • Hassold T, Hunt P (2001) To err (meiotically) is human: the genesis of human aneuploidy. Nat Rev Genet 2(4):280–291

    Article  CAS  PubMed  Google Scholar 

  • 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 118:715–729

    Article  CAS  PubMed  Google Scholar 

  • Henikoff S, Dalal Y (2005) Centromeric chromatin: what makes it unique? Curr Opin Genet Dev 15:177–184

    Article  CAS  PubMed  Google Scholar 

  • 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 10:303–315

    Article  CAS  PubMed  Google Scholar 

  • Hori T, Amano M, Suzuki A, Backer CB, Welburn JP et al (2008) CCAN makes multiple contacts with centromeric DNA to provide distinct pathways to the outer kinetochore. Cell 135:1039–1052

    Article  CAS  PubMed  Google Scholar 

  • Howman EV, Fowler KJ, Newson AJ, Redward S, MacDonald AC et al (2000) Early disruption of centromeric chromatin organization in centromere protein A (CENP-A) null mice. Proc Natl Acad Sci USA 97:1148–1153

    Article  CAS  PubMed  Google Scholar 

  • Hsu JM, Huang J, Meluh PB, Laurent BC (2003) The yeast RSC chromatin remodelling complex is required for kinetochore function in chromosome segregation. Mol Cell Biol 23(9):3202–3215

    Article  CAS  PubMed  Google Scholar 

  • Huang J, Laurent BC (2004) A role for the RSC chromatin remodeler in regulating cohesion of sister chromatid arms. Cell Cycle 3(8):973–975

    CAS  PubMed  Google Scholar 

  • Huang J, Hsu JM, Laurent BC (2004) The RSC nucleosome-remodeling complex is required for cohesin’s association with chromosome arms. Mol Cell 13(5):739–750

    Article  CAS  PubMed  Google Scholar 

  • Ishii K (2009) Conservation and divergence of centromere specification in yeast. Curr Opin Microbiol 12(6):616–622

    Article  CAS  PubMed  Google Scholar 

  • Ishii K, Ogiyama Y, Chikashige Y, Soejima S, Masuda F et al (2008) Heterochromatin integrity affects chromosome reorganization after centromere dysfunction. Science 321(5892):1088–1091

    Article  CAS  PubMed  Google Scholar 

  • Izuta H, Ikeno M, Suzuki N, Tomonaga T, Nozaki N et al (2006) Comprehensive analysis of the ICEN (interphase centromere complex) components enriched in the CENP-A chromatin of human cells. Genes Cells 11:673–684

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Jayaram M, Mehta S, Uzri D, Velmurugan S (2004) Segregation of the yeast plasmid: similarities and contrasts with bacterial plasmid partitioning. Plasmid 51:162–178

    Article  CAS  PubMed  Google Scholar 

  • Jiang J, Birchler JA, Parrott WA, Dawe RK (2003) A molecular view of plant centromeres. Trends Plant Sci 8(12):570–575

    Article  CAS  PubMed  Google Scholar 

  • Jin W, Lamb JC, Zhang W, Kolano B, Birchler JA (2008) Histone modifications associated with both A and B chromosomes of maize. Chromosome Res 16:1203–1214

    Article  CAS  PubMed  Google Scholar 

  • Kagansky A, Folco HD, Almeida R, Pidoux AL, Boukaba A et al (2009) Synthetic heterochromatin bypasses RNAi and centromeric repeats to establish functional centromeres. Science 324(5935):1716–1719

    Article  CAS  PubMed  Google Scholar 

  • Kato T, Sato N, Hayama S, Yamabuki T, Ito T et al (2007) Activation of Holliday junction recognizing protein involved in the chromosomal stability and immortality of cancer cells. Cancer Res 67:8544–8553

    Article  CAS  PubMed  Google Scholar 

  • Ketel C, Wang HS, McClellan M, Bouchonville K, Selmecki A et al (2009) Neocentromees form efficiently at multiple possible loci in Candida albicans. PLoS Genet 5(3):e1000400

    Article  PubMed  CAS  Google Scholar 

  • Kline SL, Cheeseman IM, Hori T, Fukagawa T, Desai A (2006) The human Mis12 complex is required for kinetochore assembly and proper chromosome segregation. J Cell Biol 173:9–17

    Article  CAS  PubMed  Google Scholar 

  • Kops GJ, Weaver BA, Cleveland DW (2005) On the road to cancer: aneuploidy and the mitotic checkpoint. Nat Rev Cancer 5(10):773–785

    Article  CAS  PubMed  Google Scholar 

  • Lechner J, Carbon J (1991) A 240-kd multisubunit protein complex, CBF3, is a major component of the budding yeast centromere. Cell 64(4):717–725

    Article  CAS  PubMed  Google Scholar 

  • Lermontova I, Schubert V, Fuchs J, Klatte S, Macas J, Schubert I (2006) Loading of Arabidopsis centromeric histone CENH3 occurs mainly during G2 and requires the presence of the histone fold domain. Plant Cell 18:2443–2451

    Article  CAS  PubMed  Google Scholar 

  • Liao WT, Song LB, Zhang HZ, Zhang X, Zhang L (2007) Centromere protein-H is a novel prognostic marker for nasopharyngeal carcinoma progression and overall patient survival. Clin Cancer Res 13(2):508–514

    Article  CAS  PubMed  Google Scholar 

  • Liu ST, Rattner JB, Jablonski SA, Yen TJ (2006) Mapping the assembly pathways that specify formation of the trilaminar kinetochore plates in human cells. J Cell Biol 175:41–53

    Article  CAS  PubMed  Google Scholar 

  • Maddox PS, Oegema K, Desai A, Cheeseman IM (2004) “Holo”er than thou: chromosome segregation and kinetochore function in C. elegans. Chromosome Res 12:641–653

    Article  CAS  PubMed  Google Scholar 

  • 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(6):757–763

    Article  CAS  PubMed  Google Scholar 

  • Maggert KA, Karpen GH (2000) Acquisition and metastability of centromere identity and function: sequence analysis of a human neocentromere. Genome Res 10:725–728

    Article  CAS  PubMed  Google Scholar 

  • Maggert KA, Karpen GH (2001) Neocentromere formation occurs by an activation mechanism that requires proximity to a functional centromere. Genetics 158:1615–1628

    CAS  PubMed  Google Scholar 

  • Malik HS (2006) A hitchhiker’s guide to survival finally makes CENs. J Cell Biol 174(6):747–749

    Article  CAS  PubMed  Google Scholar 

  • Marshall OJ, Choo KH (2009) Neocentromeres come of age. PLoS Genet 5(3):e1000370

    Article  PubMed  CAS  Google Scholar 

  • 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(2):261–282

    Article  CAS  PubMed  Google Scholar 

  • Masumoto H, Nakano M, Ohzeki J (2004) The role of CENP-B and alpha-satellite DNA: de novo assembly and epigenetic maintenance of human centromeres. Chromosome Res 12:543–556

    Article  CAS  PubMed  Google Scholar 

  • May BP, Lippman ZB, Fang Y, Spector DL, Martienssen RA (2005) Differential regulation of strand-specific transcripts from Arabidopsis centromeric satellite repeats. PLoS Genet 1:e79

    Article  PubMed  CAS  Google Scholar 

  • Mehta S, Yang XM, Chan CS, Dobson MJ, Jayaram M, Velmurugan S (2002) The 2 micron plasmid purloins the yeast cohesin complex: a mechanism for coupling plasmid partitioning and chromosome segregation? J Cell Biol 158(4):625–637

    Article  CAS  PubMed  Google Scholar 

  • Mellone BG, Allshire RC (2003) Stretching it: putting the CEN(P-A) in centromere. Curr Opin Genet Dev 13(2):191–198

    Article  CAS  PubMed  Google Scholar 

  • Mellone BG, Zhang W, Karpen GH (2009) Frodos found: behold the CENP-A “Ring” bearers. Cell 137:409–412

    Article  CAS  PubMed  Google Scholar 

  • Meluh PB, Yang P, Glowczewski L, Koshland D, Smith MM (1998) Cse4p is a component of the core centromere of Saccharomyces cerevisiae. Cell 94(5):607–613

    Article  CAS  PubMed  Google Scholar 

  • Milks KJ, Moree B, Straight AF (2009) Dissection of CENP-C directed centromere and kinetochore assembly. Mol Biol Cell 20(19):4246–4255

    Article  CAS  PubMed  Google Scholar 

  • 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 129:1153–1164

    Article  CAS  PubMed  Google Scholar 

  • Murphy TD, Karpen GH (1998) Centromeres take flight: α satellite and the quest for the human centromere. Cell 93:317–320

    Article  CAS  PubMed  Google Scholar 

  • Musgrave DR, Sandman KM, Reeve JN (1991) DNA binding by the archaeal histone HMf results in positive supercoiling. Proc Natl Acad Sci USA 88(23):10397–10401

    Article  CAS  PubMed  Google Scholar 

  • Mythreye K, Bloom KS (2003) Differential kinetochore protein requirements for establishment versus propagation of centromere activity in Saccharomyces cerevisiae. J Cell Biol 160(6):833–843

    Article  CAS  PubMed  Google Scholar 

  • Nakano M, Cardinale S, Noskov VN, Gassmann R, Vagnarelli P et al (2008) Inactivation of a human kinetochore by specific targeting of chromatin modifiers. Dev Cell 14(4):507–522

    Article  CAS  PubMed  Google Scholar 

  • Natsume R, Eitoku M, Akai Y, Sano N, Horikoshi M, Senda T (2007) Structure and function of the histone chaperone CIA/ASF1 complexed with histones H3 and H4. Nature 446(7133):338–341

    Article  CAS  PubMed  Google Scholar 

  • Oegema K, Desai A, Rybina S, Kirkham M, Hyman AA (2001) Functional analysis of kinetochore assembly in Caenorhabditis elegans. J Cell Biol 153(6):1209–1226

    Article  CAS  PubMed  Google Scholar 

  • Okada M, Cheeseman IM, Hori T, Okawa K, McLeod IX et al (2006) The CENP-H-I complex is required for the efficient incorporation of newly synthesized CENP-A into centromeres. Nat Cell Biol 8:446–457

    Article  CAS  PubMed  Google Scholar 

  • Okada T, Ohzeki J, Nakano M, Yoda K, Brinkley WR et al (2007) CENP-B controls centromere formation depending on the chromatin context. Cell 131:1287–1300

    Article  CAS  PubMed  Google Scholar 

  • Okada M, Okawa K, Isobe T, Fukagawa T (2009) CENP-H-containing complex facilitates centromere deposition of CENP-A in cooperation with FACT and CHD1. Mol Biol Cell 20:3986–3995

    Article  CAS  PubMed  Google Scholar 

  • Panzeri L, Landonio L, Stotz A, Philippsen P (1985) Role of conserved sequence elements in yeast centromere DNA. EMBO J 4(7):1867–1874

    CAS  PubMed  Google Scholar 

  • Papacs LA, Sun Y, Anderson EL, Sun J, Holmes SG (2004) REP3-mediated silencing in Saccharomyces cerevisiae. Genetics 166(1):79–87

    Article  CAS  PubMed  Google Scholar 

  • Pearson CG, Yeh E, Gardner M, Odde D, Salmon ED, Bloom K (2004) Stable kinetochore-microtubule attachment constrains centromere positioning in metaphase. Curr Biol 14:1962–1967

    Article  CAS  PubMed  Google Scholar 

  • Perpelescu M, Nozaki N, Obuse C, Yang H, Yoda K (2009) Active establishment of centromeric CENP-A chromatin by RSF complex. J Cell Biol 185:397–407

    Article  CAS  PubMed  Google Scholar 

  • Pidoux AL, Allshire RC (2004) Kinetochore and heterochromatin domains of the fission yeast centromere. Chromosome Res 12(6):521–534

    Article  CAS  PubMed  Google Scholar 

  • Polizzi C, Clarke L (1991) The chromatin structure of centromere formation from fission yeast: differentiation of the central core that correlates with function. J Cell Biol 112(2):191–201

    Article  CAS  PubMed  Google Scholar 

  • Rajagopalan H, Lengauer C (2004) Aneuploidy and cancer. Nature 432(7015):338–341

    Article  CAS  PubMed  Google Scholar 

  • Ray-Gallet D, Quivy JP, Scamps C, Martini EMD, Lipinski M, Almouzni G (2004) HIRA is critical for a nucleosome assembly pathway independent of DNA synthesis. Mol Cell 9(5):1091–1100

    Article  Google Scholar 

  • Régnier V, Vagnarelli P, Fukagawa T, Zerjal T, Burns E et al (2005) CENP-A is required for accurate chromosome segregation and sustained kinetochore association of BubR1. Mol Cell Biol 25(10):3967–3981

    Article  PubMed  CAS  Google Scholar 

  • Reinberg D, Sims RJ 3rd (2006) de FACTo nucleosome dynamics. J Biol Chem 281:23297–23301

    Article  CAS  PubMed  Google Scholar 

  • Rocha W, Verreault A (2008) Clothing up DNA for all seasons: histone chaperones and nucleosome assembly pathways. FEBS Lett 582:1938–1949

    Article  CAS  PubMed  Google Scholar 

  • Rosasco-Nitcher SE, Lan W, Khorasanizadeh S, Stukenberg PT (2008) Centromeric aurora-B activation requires TD-60, microtubules, and substrate priming phosphorylation. Science 319:469–472

    Article  CAS  PubMed  Google Scholar 

  • Runge KW, Wellinger RJ, Zakian VA (1991) Effect of excess centromeres and excess telomeres on chromosome loss rates. Mol Cell Biol 11(6):2919–2928

    CAS  PubMed  Google Scholar 

  • Saffery R, Irvine DV, Griffiths B, Kalitsis P, Wordeman L, Andy Choo KH (2000) Human centromeres and neocentromeres show identical distribution patterns of >20 functionally important kinetochore-associated proteins. Hum Mol Genet 9:175–185

    Article  CAS  PubMed  Google Scholar 

  • Saffery R, Sumer H, Hassan S, Wong LH, Craig JM et al (2003) Transcription within a functional human centromere. Mol Cell 12:509–516

    Article  CAS  PubMed  Google Scholar 

  • Samoshkin A, Arnaoutov A, Jansen LE, Ouspenski I, Dye L et al (2009) Human condensin function is essential for centromeric chromatin assembly and proper sister kinetochore orientation. PLoS One 4(8):e6831

    Article  PubMed  CAS  Google Scholar 

  • Sanchez-Pulido L, Pidoux AL, Ponting CP, Allshire RC (2009) Common ancestry of the CENP-A chaperones Scm3 and HJURP. Cell 137(7):1173–1174

    Article  PubMed  Google Scholar 

  • Schuh M, Lehner CF, Heidmann S (2007) Incorporation of Drosophila CID/CENP-A and CENP-C into centromeres during early embryonic anaphase. Curr Biol 17:237–243

    Article  CAS  PubMed  Google Scholar 

  • Shelby RD, Monier K, Sullivan KF (2000) Chromatin assembly at kinetochores is uncoupled from DNA replication. J Cell Biol 151:1113–1118

    Article  CAS  PubMed  Google Scholar 

  • Shuaib M, Ouararhni K, Dimitrov S, Hamiche A (2010) HJURP binds CENP-A via a highly conserved N-terminal domain and mediates its deposition at centromeres

  • Silva MCC, Jansen LET (2009) At the right place at the right time: novel CENP-A binding proteins shed light on centromere assembly. Chromosoma 118(5):567–574

    Article  CAS  PubMed  Google Scholar 

  • Smith S, Stillman B (1991) Stepwise assembly of chromatin during DNA replication in vitro. EMBO J 10(4):971–980

    CAS  PubMed  Google Scholar 

  • Sullivan BA, Karpen GH (2004) Centromeric chromatin exhibits a histone modification pattern that is distinct from euchromatin and heterochromatin. Nat Struct Mol Biol 11(11):1076–1083

    Article  CAS  PubMed  Google Scholar 

  • Sullivan BA, Willard HF (1998) Stable dicentric X chromosomes with two functional centromeres. Nat Genet 20:227–228

    Article  CAS  PubMed  Google Scholar 

  • Sutton A, Broach JR (1985) Signals for transcription initiation and termination in the Saccharomyces cerevisiae plasmid 2 micron circle. Mol Cell Biol 5(10):2770–2780

    CAS  PubMed  Google Scholar 

  • Takahashi K, Murakami S, Shikashige 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 3:819–835

    CAS  PubMed  Google Scholar 

  • 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 19:682–690

    Article  CAS  PubMed  Google Scholar 

  • Tomonaga T, Matsushita K, Yamaguchi S, Oohashi T, Shimada H et al (2003) Overexpression and mistargeting of centromere Protein-A in human primary colorectal cancer. Cancer Res 63:3511–3516

    CAS  PubMed  Google Scholar 

  • Topp CN, Zhong CX, Dawe RK (2004) Centromere-encoded RNAs are integral components of the maize kinetochore. Proc Natl Acad Sci USA 101(45):15986–15991

    Article  CAS  PubMed  Google Scholar 

  • Torras-Llort M, Moreno-Moreno O, Azorin F (2009) Focus on the centre: the role of chromatin on the regulation of centromere identity and function. EMBO J 28(16):2337–2348

    Article  CAS  PubMed  Google Scholar 

  • Trazzi S, Perini G, Bernardoni R, Zoli M, Reese JC et al (2009) The C-terminal domain of CENP-C displays multiple and critical functions for mammalian centromere formation. PLoS One 4(6):e5832

    Article  PubMed  CAS  Google Scholar 

  • Tyler-Smith C, Gimelli G, Giglio S, Floridia G, Pandya A et al (1999) Transmission of a fully functional human neocentromeres through three generations. Am J Hum Genet 64:1440–1444

    Article  CAS  PubMed  Google Scholar 

  • Vagnarelli P, Ribeiro SA, Earnshaw WC (2008) Centromeres: old tales and new tools. FEBS Lett 582:1950–1959

    Article  CAS  PubMed  Google Scholar 

  • Van Hooser AA, Ouspenski II, Gregson HC, Starr DA, Yen TJ et al (2001) Specification of kinetochore-forming chromatin by the histone H3 variant CENP-A. J Cell Sci 114(Pt 19):3529–3542

    PubMed  Google Scholar 

  • Walfridsson J, Bjerling P, Thalen M, Yoo EJ, Park SD, Ekwall K (2005) The CHD remodeling factor Hrp1 stimulates CENP-A loading to centromeres. Nucleic Acids Res 33:2868–2879

    Article  CAS  PubMed  Google Scholar 

  • Wang Ga, Zhang X, Jin W (2009) An overview of plant centromeres. J Genet Genomics 36(9):529–537

    Article  CAS  PubMed  Google Scholar 

  • Warburton PE (2004) Chromosomal dynamics of human neocentromere formation. Chromosome Res 12(6):617–626

    Article  CAS  PubMed  Google Scholar 

  • Williams SK, Tyler JK (2007) Transcriptional regulation by chromatin disassembly and reassembly. Curr Opin Genet Dev 17:88–93

    Article  CAS  PubMed  Google Scholar 

  • Williams BC, Murphy TD, Goldberg ML, Karpen GH (1998) Neocentromere activity of structurally acentric mini-chromosomes in Drosophila. Nat Genet 18:30–38

    Article  CAS  PubMed  Google Scholar 

  • Williams JS, Hayashi T, Yanagida M, Russell P (2009) Fission yeast Scm3 mediates stable assembly of Cnp1/CENP-A into centromeric chromatin. Mol Cell 33(3):287–298

    Article  CAS  PubMed  Google Scholar 

  • Wong MC, Scott-Drew SR, Hayes MJ, Howard PJ, Murray JA (2002) RSC2, encoding a component of the RSC nucleosome remodeling complex, is essential for 2 microm plasmid maintenance in Saccharomyces cerevisiae. Mol Cell Biol 22(12):4218–4229

    Article  CAS  PubMed  Google Scholar 

  • Wong NC, Wong LH, Quach JM, Canham P, Craig JM et al (2006) Permissive transcriptional activity at the centromere through pockets of DNA hypomethylation. PLoS Genet 2(2):e17

    Article  PubMed  CAS  Google Scholar 

  • Wood V, Gwilliam R, Rajandream MA, Lyne M, Lyne R et al (2002) The genome sequence of Schizosachharomyces pombe. Nature 415:871–880

    Article  CAS  PubMed  Google Scholar 

  • Yan H, Ito H, Nobuta K, Ouyang S, Jin W et al (2006) Genomic and genetic characterization of rice Cen3 reveals extensive transcription and evolutionary implications of a complex centromere. Plant Cell 18(9):2123–2133

    Article  CAS  PubMed  Google Scholar 

  • Yang XM, Mehta S, Uzri D, Jayaram M, Velmurugan S (2004) Mutations in a partitioning protein and altered chromatin structure at the partitioning locus prevent cohesin recruitment by the Saccharomyces cerevisiae plasmid and cause plasmid missegregation. Mol Cell Biol 24(12):5290–5303

    Article  CAS  PubMed  Google Scholar 

  • Yuen KWY, Montpetit B, Hieter P (2005) The kinetochore and cancer: what’s the connection? Curr Opin Cell Biol 17:576–582

    Article  CAS  PubMed  Google Scholar 

  • Zeitlin SG, Shelby RD, Sullivan KF (2001) CENP-A is phosphorylatedby Aurora B kinase and plays an unexpected role in completion of cytokinesis. J Cell Biol 155(7):1147–1157

    Article  CAS  PubMed  Google Scholar 

  • Zeitlin SG, Baker NM, Chapados BR, Soutoglou E, Wang JYJ, Berns MW, Cleveland DW (2009) Double-strand DNA breaks recruit the centromeric histone CENP-A. PNAS 106(37):15762–15767

    Article  CAS  PubMed  Google Scholar 

  • 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(1):25–34

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We acknowledge Sujata Hajra for a critical reading of the manuscript. We regret not being able to refer to the work of everyone in the field. We are grateful to the reviewers for their insightful critique that helped improve the article’s style and content. G.D.M. and M.P.A. are supported by CSIR fellowships (20-6/2009(i)EU-IV/329667, EU-IV/2008/JUNE/327214, respectively). SKG laboratory is supported by start-up grant from the Indian Institute of Technology, Bombay, India.

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  1. Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, 400076, India

    Gunjan D. Mehta, Meenakshi P. Agarwal & Santanu Kumar Ghosh

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  1. Gunjan D. Mehta
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  2. Meenakshi P. Agarwal
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  3. Santanu Kumar Ghosh
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Correspondence to Santanu Kumar Ghosh.

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Communicated by T. Nyström.

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Mehta, G.D., Agarwal, M.P. & Ghosh, S.K. Centromere identity: a challenge to be faced. Mol Genet Genomics 284, 75–94 (2010). https://doi.org/10.1007/s00438-010-0553-4

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Keywords

  • Centromere
  • Epigenetics
  • CENP-A
  • Histone modification
  • Chromosome