Advertisement

Chromosoma

, Volume 126, Issue 5, pp 559–575 | Cite as

Using human artificial chromosomes to study centromere assembly and function

  • Oscar Molina
  • Natalay Kouprina
  • Hiroshi Masumoto
  • Vladimir Larionov
  • William C. Earnshaw
Review

Abstract

Centromeres are the site of assembly of the kinetochore, which directs chromosome segregation during cell division. Active centromeres are characterized by the presence of nucleosomes containing CENP-A and a specific chromatin environment that resembles that of active genes. Recent work using human artificial chromosomes (HAC) sheds light on the fine balance of different histone post-translational modifications and transcription that exists at centromeres for kinetochore assembly and maintenance. Here, we review the use of HAC technology to understand centromere assembly and function. We put particular emphasis on studies using the alphoidtetO HAC, whose centromere can be specifically modified for epigenetic engineering studies.

Keywords

Human artificial chromosomes Centromere Kinetochore CENP-A Mitosis 

Notes

Compliance with ethical standards

Funding

This work was supported by the Wellcome Trust, of which W.C.E. is a Principal Research Fellow (grant number 073915). O.M. was funded by the European Molecular Biology Organization (long-term EMBO fellowship; ALTF-453-2012). The Intramural Research Program of the NIH, NCI Center for Cancer Research (V.L. and N.K.) and MEXT KAKENHI grant numbers 23247030, 23114008 and the Kazusa DNA Research Institute Foundation (H.M.).

Conflict of interests

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

References

  1. Akiyoshi B, Gull K (2013) Evolutionary cell biology of chromosome segregation: insights from trypanosomes. Open biology 3:130023. doi: 10.1098/rsob.130023 PubMedPubMedCentralCrossRefGoogle Scholar
  2. Alabert C, Groth A (2012) Chromatin replication and epigenome maintenance Nature reviews. Molecular cell biology 13:153–167. doi: 10.1038/nrm3288 PubMedGoogle Scholar
  3. Aldrup-Macdonald ME, Sullivan BA (2014) The past, present, and future of human centromere genomics. Genes 5:33–50PubMedPubMedCentralCrossRefGoogle Scholar
  4. Alonso A et al (2007) Co-localization of CENP-C and CENP-H to discontinuous domains of CENP-A chromatin at human neocentromeres. Genome Biol 8:R148. doi: 10.1186/gb-2007-8-7-r148 PubMedPubMedCentralCrossRefGoogle Scholar
  5. 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 Human molecular. Genetics 12:2711–2721. doi: 10.1093/hmg/ddg282 Google Scholar
  6. Allshire RC, Ekwall K (2015) Epigenetic Regulation of Chromatin States in Schizosaccharomyces pombe Cold Spring Harbor. perspectives in biology 7:a018770. doi: 10.1101/cshperspect.a018770 PubMedPubMedCentralGoogle Scholar
  7. Allshire RC, Karpen GH (2008) Epigenetic regulation of centromeric chromatin: old dogs, new tricks? Nat Rev Genet 9:923–937. doi: 10.1038/nrg2466 PubMedPubMedCentralCrossRefGoogle Scholar
  8. Amano M, Suzuki A, Hori T, Backer C, Okawa K, Cheeseman IM, Fukagawa T (2009) The CENP-S complex is essential for the stable assembly of outer kinetochore structure. J Cell Biol 186:173–182. doi: 10.1083/jcb.200903100 PubMedPubMedCentralCrossRefGoogle Scholar
  9. Barnhart MC, Kuich PH, Stellfox ME, Ward JA, Bassett EA, Black BE, Foltz DR (2011) HJURP is a CENP-A chromatin assembly factor sufficient to form a functional de novo kinetochore. J Cell Biol 194:229–243. doi: 10.1083/jcb.201012017 PubMedPubMedCentralCrossRefGoogle Scholar
  10. Basu J, Stromberg G, Compitello G, Willard HF, Van Bokkelen G (2005) Rapid creation of BAC-based human artificial chromosome vectors by transposition with synthetic alpha-satellite arrays. Nucleic Acids Res 33:587–596. doi: 10.1093/nar/gki207 PubMedPubMedCentralCrossRefGoogle Scholar
  11. Basu J, Willard HF (2006) Human artificial chromosomes: potential applications and clinical considerations. Pediatr Clin N Am 53:843–853. doi: 10.1016/j.pcl.2006.08.013 CrossRefGoogle Scholar
  12. Berger SL (2007) The complex language of chromatin regulation during transcription. Nature 447:407–412. doi: 10.1038/nature05915 PubMedCrossRefGoogle Scholar
  13. Bergmann JH et al (2012a) Epigenetic engineering: histone H3K9 acetylation is compatible with kinetochore structure and function. J Cell Sci 125:411–421. doi: 10.1242/jcs.090639 PubMedPubMedCentralCrossRefGoogle Scholar
  14. Bergmann JH, Martins NM, Larionov V, Masumoto H, Earnshaw WC (2012b) HACking the centromere chromatin code: insights from human artificial chromosomes Chromosome research. an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology 20:505–519. doi: 10.1007/s10577-012-9293-0 CrossRefGoogle Scholar
  15. Bergmann JH et al (2011) Epigenetic engineering shows H3K4me2 is required for HJURP targeting and CENP-A assembly on a synthetic human kinetochore. EMBO J 30:328–340. doi: 10.1038/emboj.2010.329 PubMedCrossRefGoogle Scholar
  16. Bernard P, Maure JF, Partridge JF, Genier S, Javerzat JP, Allshire RC (2001) Requirement of heterochromatin for cohesion at centromeres. Science 294:2539–2542. doi: 10.1126/science.1064027 PubMedCrossRefGoogle Scholar
  17. Black BE (2011) Cleveland DW. Epigenetic centromere propagation and the nature of CENP-a nucleosomes Cell 144:471–479. doi: 10.1016/j.cell.2011.02.002 PubMedGoogle Scholar
  18. Blower MD, Sullivan BA, Karpen GH (2002) Conserved organization of centromeric chromatin in flies and humans Developmental. Cell 2:319–330Google Scholar
  19. Bodor DL et al (2014) The quantitative architecture of centromeric. chromatin eLife 3:e02137. doi: 10.7554/eLife.02137 PubMedGoogle Scholar
  20. Booth DG et al (2016) 3D-CLEM Reveals that a Major Portion of Mitotic Chromosomes Is Not Chromatin. Mol Cell 64:790–802. doi: 10.1016/j.molcel.2016.10.009 PubMedPubMedCentralCrossRefGoogle Scholar
  21. Brinkley BR, Stubblefield E (1966) The fine structure of the kinetochore of a mammalian cell in vitro. Chromosoma 19:28–43PubMedCrossRefGoogle Scholar
  22. Brown KE, Barnett MA, Burgtorf C, Shaw P, Buckle VJ, Brown WR (1994) Dissecting the centromere of the human Y chromosome with cloned telomeric DNA Human molecular. Genetics 3:1227–1237Google Scholar
  23. Cardinale S et al (2009) Hierarchical inactivation of a synthetic human kinetochore by a chromatin modifier. Mol Biol Cell 20:4194–4204. doi: 10.1091/mbc.E09-06-0489 PubMedPubMedCentralCrossRefGoogle Scholar
  24. Carroll CW, Milks KJ, Straight AF (2010) Dual recognition of CENP-A nucleosomes is required for centromere assembly. J Cell Biol 189:1143–1155. doi: 10.1083/jcb.201001013 PubMedPubMedCentralCrossRefGoogle Scholar
  25. Catania S, Allshire RC (2014) Anarchic centromeres: deciphering order from apparent chaos Current opinion in cell. Biology 26:41–50. doi: 10.1016/j.ceb.2013.09.004 Google Scholar
  26. Catania S, Pidoux AL, Allshire RC (2015) Sequence features and transcriptional stalling within centromere DNA promote establishment of CENP-A chromatin. PLoS Genet 11:e1004986. doi: 10.1371/journal.pgen.1004986 PubMedPubMedCentralCrossRefGoogle Scholar
  27. Clarke L, Baum MP (1990) Functional analysis of a centromere from fission yeast: a role for centromere-specific repeated DNA sequences. Mol Cell Biol 10:1863–1872PubMedPubMedCentralCrossRefGoogle Scholar
  28. Clarke L, Carbon J (1980) Isolation of a yeast centromere and construction of functional small circular chromosomes. Nature 287:504–509PubMedCrossRefGoogle Scholar
  29. Cleveland DW, Mao Y, Sullivan KF (2003) Centromeres and kinetochores: from epigenetics to mitotic checkpoint signaling. Cell 112:407–421PubMedCrossRefGoogle Scholar
  30. 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 9:3342–3349PubMedPubMedCentralCrossRefGoogle Scholar
  31. Chan FL, Marshall OJ, Saffery R, Kim BW, Earle E, Choo KH, Wong LH (2012) Active transcription and essential role of RNA polymerase II at the centromere during mitosis. Proc Natl Acad Sci U S A 109:1979–1984. doi: 10.1073/pnas.1108705109 PubMedPubMedCentralCrossRefGoogle Scholar
  32. Cheeseman IM, Desai A (2008) Molecular architecture of the kinetochore-microtubule interface Nature reviews Molecular cell. Biology 9:33–46. doi: 10.1038/nrm2310 Google Scholar
  33. Cheeseman IM, Hori T, Fukagawa T, Desai A (2008) KNL1 and the CENP-H/I/K complex coordinately direct kinetochore assembly in vertebrates Molecular biology of the cell 19:587–594 doi: 10.1091/mbc.E07-10-1051
  34. Choo KH, Vissel B, Nagy A, Earle E, Kalitsis P (1991) A survey of the genomic distribution of alpha satellite DNA on all the human chromosomes, and derivation of a new consensus sequence. Nucleic Acids Res 19:1179–1182PubMedPubMedCentralCrossRefGoogle Scholar
  35. Desai A, Rybina S, Muller-Reichert T, Shevchenko A, Shevchenko A, Hyman A, Oegema K (2003) KNL-1 directs assembly of the microtubule-binding interface of the kinetochore in C. elegans Genes & development 17:2421–2435. doi: 10.1101/gad.1126303 CrossRefGoogle Scholar
  36. Dinant C, Houtsmuller AB, Vermeulen W (2008) Chromatin structure and DNA damage repair. Epigenetics Chromatin 1:9. doi: 10.1186/1756-8935-1-9 PubMedPubMedCentralCrossRefGoogle Scholar
  37. Doheny KF, Sorger PK, Hyman AA, Tugendreich S, Spencer F, Hieter P (1993) Identification of essential components of the S. cerevisiae kinetochore. Cell 73:761–774PubMedCrossRefGoogle Scholar
  38. Drinnenberg IA, de Young D, Henikoff S, Malik HS (2014) Recurrent loss of CenH3 is associated with independent transitions to holocentricity in insects eLife 3 doi: 10.7554/eLife.03676
  39. du Sart D et al (1997) A functional neo-centromere formed through activation of a latent human centromere and consisting of non-alpha-satellite. DNA Nature genetics 16:144–153. doi: 10.1038/ng0697-144 PubMedCrossRefGoogle Scholar
  40. Duffy S et al (2016) Overexpression screens identify conserved dosage chromosome instability genes in yeast and human cancer. Proc Natl Acad Sci U S A 113:9967–9976. doi: 10.1073/pnas.1611839113 PubMedPubMedCentralCrossRefGoogle Scholar
  41. Dunleavy EM et al (2009) HJURP is a cell-cycle-dependent maintenance and deposition factor of CENP-A at centromeres. Cell 137:485–497. doi: 10.1016/j.cell.2009.02.040 PubMedCrossRefGoogle Scholar
  42. Earnshaw WC, Cooke CA (1989) Proteins of the inner and outer centromere of mitotic chromosomes Genome / National Research Council. Canada = Genome / Conseil national de recherches Canada 31:541–552CrossRefGoogle Scholar
  43. Earnshaw WC, Migeon BR (1985) Three related centromere proteins are absent from the inactive centromere of a stable isodicentric. Chromosome Chromosoma 92:290–296PubMedCrossRefGoogle Scholar
  44. 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
  45. Earnshaw WC, Rattner JB (1991) The use of autoantibodies in the study of nuclear and chromosomal organization. Methods Cell Biol 35:135–175PubMedCrossRefGoogle Scholar
  46. 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
  47. Ebersole T et al (2005) Rapid generation of long synthetic tandem repeats and its application for analysis in human artificial chromosome formation. Nucleic Acids Res 33:e130. doi: 10.1093/nar/gni129 PubMedPubMedCentralCrossRefGoogle 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. Ernst J, Kellis M (2010) Discovery and characterization of chromatin states for systematic annotation of the human genome Nature. Biotechnology 28:817–825. doi: 10.1038/nbt.1662 Google Scholar
  50. Fachinetti D et al (2013) A two-step mechanism for epigenetic specification of centromere identity and function. Nat Cell Biol 15:1056–1066. doi: 10.1038/ncb2805 PubMedPubMedCentralCrossRefGoogle Scholar
  51. Farr CJ, Bayne RA, Kipling D, Mills W, Critcher R, Cooke HJ (1995) Generation of a human X-derived minichromosome using telomere-associated chromosome fragmentation. EMBO J 14:5444–5454PubMedPubMedCentralGoogle Scholar
  52. 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. doi: 10.1126/science.1150944 PubMedPubMedCentralCrossRefGoogle Scholar
  53. Foltz DR et al (2009) Centromere-specific assembly of CENP-a nucleosomes is mediated by HJURP. Cell 137:472–484. doi: 10.1016/j.cell.2009.02.039 PubMedPubMedCentralCrossRefGoogle Scholar
  54. Foltz DR, Jansen LE, Black BE, Bailey AO, Yates JR 3rd, Cleveland DW (2006) The human CENP-A centromeric nucleosome-associated complex Nature. cell biology 8:458–469. doi: 10.1038/ncb1397 PubMedGoogle Scholar
  55. Frias C, Pampalona J, Genesca A, Tusell L (2012) Telomere dysfunction and genome instability. Front Biosci 17:2181–2196CrossRefGoogle Scholar
  56. Friedman JR, Fredericks WJ, Jensen DE, Speicher DW, Huang XP, Neilson EG, Rauscher FJ 3rd (1996) KAP-1, a novel corepressor for the highly conserved KRAB repression domain. Genes Dev 10:2067–2078PubMedCrossRefGoogle Scholar
  57. Fujita R et al (2015) Stable complex formation of CENP-B with the CENP-A nucleosome. Nucleic Acids Res 43:4909–4922. doi: 10.1093/nar/gkv405 PubMedPubMedCentralCrossRefGoogle Scholar
  58. 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 Developmental. Cell 12:17–30. doi: 10.1016/j.devcel.2006.11.002 Google Scholar
  59. Fukagawa T, Earnshaw WC (2014a) The centromere: chromatin foundation for the kinetochore machinery Developmental. Cell 30:496–508. doi: 10.1016/j.devcel.2014.08.016 Google Scholar
  60. Fukagawa T, Earnshaw WC (2014b) Neocentromeres Current biology : CB 24:R946–R947. doi: 10.1016/j.cub.2014.08.032 PubMedCrossRefGoogle Scholar
  61. Gartenberg M (2009) Heterochromatin and the cohesion of sister chromatids Chromosome research. an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology 17:229–238. doi: 10.1007/s10577-008-9012-z CrossRefGoogle Scholar
  62. Goldberg IG, Sawhney H, Pluta AF, Warburton PE, Earnshaw WC (1996) Surprising deficiency of CENP-B binding sites in African green monkey alpha-satellite DNA: implications for CENP-B function at centromeres. Mol Cell Biol 16:5156–5168PubMedPubMedCentralCrossRefGoogle Scholar
  63. Goshima G, Kiyomitsu T, Yoda K, Yanagida M (2003) Human centromere chromatin protein hMis12, essential for equal segregation, is independent of CENP-A loading pathway. J Cell Biol 160:25–39. doi: 10.1083/jcb.200210005 PubMedPubMedCentralCrossRefGoogle Scholar
  64. Grimes BR, Schindelhauer D, McGill NI, Ross A, Ebersole TA, Cooke HJ (2001) Stable gene expression from a mammalian artificial chromosome. EMBO Rep 2:910–914. doi: 10.1093/embo-reports/kve187 PubMedPubMedCentralCrossRefGoogle Scholar
  65. 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 15:345–355. doi: 10.1038/ng0497-345 PubMedCrossRefGoogle Scholar
  66. Hegemann JH, Fleig UN (1993) The centromere of budding yeast BioEssays : news and reviews in molecular, cellular and developmental. Biology 15:451–460. doi: 10.1002/bies.950150704 Google Scholar
  67. Heller R, Brown KE, Burgtorf C, Brown WR (1996) Mini-chromosomes derived from the human Y chromosome by telomere directed chromosome breakage Proceedings of the National. Academy of Sciences of the United States of America 93:7125–7130CrossRefGoogle Scholar
  68. 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 U S A 96:592–597PubMedPubMedCentralCrossRefGoogle Scholar
  69. Hill A, Bloom K (1987) Genetic manipulation of centromere function. Mol Cell Biol 7:2397–2405PubMedPubMedCentralCrossRefGoogle Scholar
  70. Hori T et al (2008) CCAN makes multiple contacts with centromeric DNA to provide distinct pathways to the outer kinetochore. Cell 135:1039–1052. doi: 10.1016/j.cell.2008.10.019 PubMedCrossRefGoogle Scholar
  71. Hori T, Shang WH, Takeuchi K, Fukagawa T (2013) The CCAN recruits CENP-A to the centromere and forms the structural core for kinetochore assembly. J Cell Biol 200:45–60. doi: 10.1083/jcb.201210106 PubMedPubMedCentralCrossRefGoogle Scholar
  72. Hori T et al (2014) Histone H4 Lys 20 monomethylation of the CENP-A nucleosome is essential for kinetochore assembly. Dev Cell 29:740–749. doi: 10.1016/j.devcel.2014.05.001 PubMedPubMedCentralCrossRefGoogle Scholar
  73. Hudson DF et al (1998) Centromere protein B null mice are mitotically and meiotically normal but have lower body and testis weights. J Cell Biol 141:309–319PubMedPubMedCentralCrossRefGoogle Scholar
  74. Iida Y et al (2014) Bi-HAC vector system toward gene and cell therapy ACS synthetic. Biology 3:83–90. doi: 10.1021/sb400166j Google Scholar
  75. Ikeno M et al (1998) Construction of YAC-based mammalian artificial chromosomes. Nat Biotechnol 16:431–439. doi: 10.1038/nbt0598-431 PubMedCrossRefGoogle Scholar
  76. Ikeno M, Inagaki H, Nagata K, Morita M, Ichinose H, Okazaki T (2002) Generation of human artificial chromosomes expressing naturally controlled guanosine triphosphate cyclohydrolase I gene Genes to cells. devoted to molecular & cellular mechanisms 7:1021–1032CrossRefGoogle Scholar
  77. Ikeno M, Masumoto H, Okazaki T (1994) Distribution of CENP-B boxes reflected in CREST centromere antigenic sites on long-range alpha-satellite DNA arrays of human chromosome 21 Human molecular. Genetics 3:1245–1257Google Scholar
  78. Jansen LE, Black BE, Foltz DR, Cleveland DW (2007) Propagation of centromeric chromatin requires exit from mitosis. J Cell Biol 176:795–805. doi: 10.1083/jcb.200701066 PubMedPubMedCentralCrossRefGoogle Scholar
  79. Jokelainen PT (1967) The ultrastructure and spatial organization of the metaphase kinetochore in mitotic rat cells. J Ultrastruct Res 19:19–44PubMedCrossRefGoogle Scholar
  80. Kagansky A et al (2009) Synthetic heterochromatin bypasses RNAi and centromeric repeats to establish functional centromeres. Science 324:1716–1719. doi: 10.1126/science.1172026 PubMedPubMedCentralCrossRefGoogle Scholar
  81. Kanellopoulou C et al (2005) Dicer-deficient mouse embryonic stem cells are defective in differentiation and centromeric silencing. Genes Dev 19:489–501. doi: 10.1101/gad.1248505 PubMedPubMedCentralCrossRefGoogle Scholar
  82. Kapoor M et al (1998) The cenpB gene is not essential in mice. Chromosoma 107:570–576PubMedCrossRefGoogle Scholar
  83. Karpen GH, Allshire RC (1997) The case for epigenetic effects on centromere identity and function Trends in genetics : TIG 13:489–496PubMedGoogle Scholar
  84. Kazuki Y et al (2011) Refined human artificial chromosome vectors for gene therapy and animal transgenesis. Gene Ther 18:384–393. doi: 10.1038/gt.2010.147 PubMedCrossRefGoogle Scholar
  85. Kim JH et al (2011) Human artificial chromosome (HAC) vector with a conditional centromere for correction of genetic deficiencies in human cells. Proc Natl Acad Sci U S A 108:20048–20053. doi: 10.1073/pnas.1114483108 PubMedPubMedCentralCrossRefGoogle Scholar
  86. Kim JH et al. (2016) Development of a novel HAC-based "gain of signal" quantitative assay for measuring chromosome instability (CIN) in cancer cellsGoogle Scholar
  87. Kononenko AV et al. (2014) A portable BRCA1-HAC (human artificial chromosome) module for analysis of BRCA1 tumor suppressor function Nucleic acids research 42 doi: 10.1093/nar/gku870
  88. Kouprina N, Earnshaw WC, Masumoto H, Larionov V (2013) A new generation of human artificial chromosomes for functional genomics and gene therapy Cellular and molecular life sciences. CMLS 70:1135–1148. doi: 10.1007/s00018-012-1113-3 PubMedCrossRefGoogle Scholar
  89. Kouprina N et al (2003) Cloning of human centromeres by transformation-associated recombination in yeast and generation of functional human artificial chromosomes. Nucleic Acids Res 31:922–934PubMedPubMedCentralCrossRefGoogle Scholar
  90. Kouprina N, Larionov V (2016) Transformation-associated recombination (TAR) cloning for genomics studies and synthetic biology. Chromosoma 125:621–632. doi: 10.1007/s00412-016-0588-3 PubMedPubMedCentralCrossRefGoogle Scholar
  91. Kouprina N et al (2012) Organization of synthetic alphoid DNA array in human artificial chromosome (HAC) with a conditional centromere ACS synthetic. Biology 1:590–601. doi: 10.1021/sb3000436 Google Scholar
  92. Kouprina N, Tomilin AN, Masumoto H, Earnshaw WC, Larionov V (2014) Human artificial chromosome-based gene delivery vectors for biomedicine and biotechnology. Expert opinion on drug delivery 11:517–535. doi: 10.1517/17425247.2014.882314 PubMedCrossRefGoogle Scholar
  93. Kugou K, Hirai H, Masumoto H, Koga A (2016) Formation of functional CENP-B boxes at diverse locations in repeat units of centromeric DNA in New World monkeys. Sci Rep 6:27833. doi: 10.1038/srep27833 PubMedPubMedCentralCrossRefGoogle Scholar
  94. Kwon MS, Hori T, Okada M, Fukagawa T (2007) CENP-C is involved in chromosome segregation, mitotic checkpoint function, and kinetochore assembly. Mol Biol Cell 18:2155–2168. doi: 10.1091/mbc.E07-01-0045 PubMedPubMedCentralCrossRefGoogle Scholar
  95. Lahtz C, Pfeifer GP (2011) Epigenetic changes of DNA repair genes in cancer. J Mol Cell Biol 3:51–58. doi: 10.1093/jmcb/mjq053 PubMedPubMedCentralCrossRefGoogle Scholar
  96. Lee HS et al (2013) A new assay for measuring chromosome instability (CIN) and identification of drugs that elevate CIN in cancer cells. BMC Cancer 13:252. doi: 10.1186/1471-2407-13-252 PubMedPubMedCentralCrossRefGoogle Scholar
  97. Lee HS et al (2016) Effects of Anticancer Drugs on Chromosome Instability and New Clinical Implications for Tumor-Suppressing Therapies. Cancer Res 76:902–911. doi: 10.1158/0008-5472.CAN-15-1617 PubMedPubMedCentralCrossRefGoogle Scholar
  98. Liu H, Qu Q, Warrington R, Rice A, Cheng N, Yu H (2015) Mitotic Transcription Installs Sgo1 at Centromeres to Coordinate Chromosome Segregation Molecular. Cell 59:426–436. doi: 10.1016/j.molcel.2015.06.018 Google Scholar
  99. 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. doi: 10.1083/jcb.200606020 PubMedPubMedCentralCrossRefGoogle Scholar
  100. Lo AW et al (2001) A 330 kb CENP-A binding domain and altered replication timing at a human neocentromere. EMBO J 20:2087–2096. doi: 10.1093/emboj/20.8.2087 PubMedPubMedCentralCrossRefGoogle Scholar
  101. Luykx P (1965) The structure of the kinetochore in meiosis and mitosis in Urechis eggs. Exp Cell Res 39:643–657PubMedCrossRefGoogle Scholar
  102. 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 176:757–763. doi: 10.1083/jcb.200701065 PubMedPubMedCentralCrossRefGoogle Scholar
  103. Maiato H, Sampaio P, Sunkel CE (2004) Microtubule-associated proteins and their essential roles during mitosis. Int Rev Cytol 241:53–153. doi: 10.1016/S0074-7696(04)41002-X PubMedCrossRefGoogle Scholar
  104. Mandegar MA et al (2011) Functional human artificial chromosomes are generated and stably maintained in human embryonic stem cells. Hum Mol Genet 20:2905–2913. doi: 10.1093/hmg/ddr144 PubMedPubMedCentralCrossRefGoogle Scholar
  105. Martins NM, Bergmann JH, Shono N, Kimura H, Larionov V, Masumoto H, Earnshaw WC (2016) Epigenetic engineering shows that a human centromere resists silencing mediated by H3K27me3/K9me3. Mol Biol Cell 27:177–196. doi: 10.1091/mbc.E15-08-0605 PubMedPubMedCentralCrossRefGoogle Scholar
  106. 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
  107. 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
  108. Mejia JE, Larin Z (2000) The assembly of large BACs by in vivo recombination. Genomics 70:165–170. doi: 10.1006/geno.2000.6372 PubMedCrossRefGoogle Scholar
  109. Mejia JE, Willmott A, Levy E, Earnshaw WC, Larin Z (2001) Functional complementation of a genetic deficiency with human artificial chromosomes. Am J Hum Genet 69:315–326. doi: 10.1086/321977 PubMedPubMedCentralCrossRefGoogle Scholar
  110. Merry DE, Pathak S, Hsu TC (1985) Brinkley BR. Anti-kinetochore antibodies: use as probes for inactive centromeres American journal of human genetics 37:425–430PubMedGoogle Scholar
  111. Mills W, Critcher R, Lee C, Farr CJ (1999) Generation of an approximately 2.4 Mb human X centromere-based minichromosome by targeted telomere-associated chromosome fragmentation in DT40. Hum Mol Genet 8:751–761PubMedCrossRefGoogle Scholar
  112. Molina O, Carmena M, Maudlin IE, Earnshaw WC (2016a) PREditOR: a synthetic biology approach to removing heterochromatin from cells Chromosome research. an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology 24:495–509. doi: 10.1007/s10577-016-9539-3 CrossRefGoogle Scholar
  113. Molina O et al (2016b) Epigenetic engineering reveals a balance between histone modifications and transcription in kinetochore maintenance. Nat Commun 7:13334. doi: 10.1038/ncomms13334 PubMedPubMedCentralCrossRefGoogle Scholar
  114. Moralli D, Monaco ZL (2015) Developing de novo human artificial chromosomes in embryonic stem cells using HSV-1 amplicon technology Chromosome research : an international journal on the molecular. supramolecular and evolutionary aspects of chromosome biology 23:105–110. doi: 10.1007/s10577-014-9456-2 CrossRefGoogle Scholar
  115. Moralli D, Simpson KM, Wade-Martins R, Monaco ZL (2006) A novel human artificial chromosome gene expression system using herpes simplex virus type 1 vectors. EMBO Rep 7:911–918. doi: 10.1038/sj.embor.7400768 PubMedPubMedCentralCrossRefGoogle Scholar
  116. Murray AW, Szostak JW (1983) Construction of artificial chromosomes in yeast Nature 305:189–193PubMedGoogle Scholar
  117. Nakano M et al (2008) Inactivation of a human kinetochore by specific targeting of chromatin modifiers. Dev Cell 14:507–522. doi: 10.1016/j.devcel.2008.02.001 PubMedPubMedCentralCrossRefGoogle Scholar
  118. Neil DL, Villasante A, Fisher RB, Vetrie D, Cox B, Tyler-Smith C (1990) Structural instability of human tandemly repeated DNA sequences cloned in yeast artificial chromosome vectors. Nucleic Acids Res 18:1421–1428PubMedPubMedCentralCrossRefGoogle Scholar
  119. Nishino T, Rago F, Hori T, Tomii K, Cheeseman IM, Fukagawa T (2013) CENP-T provides a structural platform for outer kinetochore assembly. EMBO J 32:424–436. doi: 10.1038/emboj.2012.348 PubMedPubMedCentralCrossRefGoogle Scholar
  120. Nishino T et al (2012) CENP-T-W-S-X forms a unique centromeric chromatin structure with a histone-like fold. Cell 148:487–501. doi: 10.1016/j.cell.2011.11.061 PubMedPubMedCentralCrossRefGoogle Scholar
  121. Nonaka N, Kitajima T, Yokobayashi S, Xiao G, Yamamoto M, Grewal SI, Watanabe Y (2002) Recruitment of cohesin to heterochromatic regions by Swi6/HP1 in fission yeast. Nat Cell Biol 4:89–93. doi: 10.1038/ncb739 PubMedCrossRefGoogle Scholar
  122. Oegema K, Desai A, Rybina S, Kirkham M, Hyman AA (2001) Functional analysis of kinetochore assembly in Caenorhabditis elegans. J Cell Biol 153:1209–1226PubMedPubMedCentralCrossRefGoogle Scholar
  123. Ohzeki J et al (2012) Breaking the HAC Barrier: histone H3K9 acetyl/methyl balance regulates CENP-A assembly. EMBO J 31:2391–2402. doi: 10.1038/emboj.2012.82 PubMedPubMedCentralCrossRefGoogle Scholar
  124. Ohzeki J, Larionov V, Earnshaw WC, Masumoto H (2015) Genetic and epigenetic regulation of centromeres: a look at HAC formation Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome. Biology 23:87–103. doi: 10.1007/s10577-015-9470-z Google Scholar
  125. 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 159:765–775. doi: 10.1083/jcb.200207112 PubMedPubMedCentralCrossRefGoogle Scholar
  126. Ohzeki J et al (2016) KAT7/HBO1/MYST2 Regulates CENP-A Chromatin Assembly by Antagonizing Suv39h1-Mediated Centromere Inactivation Developmental. Cell 37:413–427. doi: 10.1016/j.devcel.2016.05.006 Google Scholar
  127. Okada M et al (2006) The CENP-H-I complex is required for the efficient incorporation of newly synthesized CENP-A into centromeres Nature. cell biology 8:446–457. doi: 10.1038/ncb1396 PubMedGoogle Scholar
  128. 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 131:1287–1300. doi: 10.1016/j.cell.2007.10.045 PubMedCrossRefGoogle Scholar
  129. Okamoto Y, Nakano M, Ohzeki J, Larionov V, Masumoto H (2007) A minimal CENP-A core is required for nucleation and maintenance of a functional human centromere. EMBO J 26:1279–1291. doi: 10.1038/sj.emboj.7601584 PubMedPubMedCentralCrossRefGoogle Scholar
  130. Olszak AM et al (2011) Heterochromatin boundaries are hotspots for de novo kinetochore formation. Nat Cell Biol 13:799–808. doi: 10.1038/ncb2272 PubMedCrossRefGoogle Scholar
  131. Oshimura M, Uno N, Kazuki Y, Katoh M, Inoue T (2015) A pathway from chromosome transfer to engineering resulting in human and mouse artificial chromosomes for a variety of applications to bio-medical challenges Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome. Biology 23:111–133. doi: 10.1007/s10577-014-9459-z Google Scholar
  132. 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 U S A 88:3734–3738PubMedPubMedCentralCrossRefGoogle Scholar
  133. 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
  134. Pearson CG, Yeh E, Gardner M, Odde D, Salmon ED, Bloom K (2004) Stable kinetochore-microtubule attachment constrains centromere positioning in metaphase. Current biology : CB 14:1962–1967. doi: 10.1016/j.cub.2004.09.086 PubMedCrossRefGoogle Scholar
  135. Perez-Castro AV, Shamanski FL, Meneses JJ, Lovato TL, Vogel KG, Moyzis RK, Pedersen R (1998) Centromeric protein B null mice are viable with no apparent abnormalities. Dev Biol 201:135–143. doi: 10.1006/dbio.1998.9005 PubMedCrossRefGoogle Scholar
  136. Perpelescu M, Fukagawa T (2011) The ABCs of CENPs Chromosoma 120:425–446. doi: 10.1007/s00412-011-0330-0 PubMedCrossRefGoogle Scholar
  137. Pertile MD, Graham AN, Choo KH, Kalitsis P (2009) Rapid evolution of mouse Y centromere repeat DNA belies recent sequence stability. Genome Res 19:2202–2213. doi: 10.1101/gr.092080.109 PubMedPubMedCentralCrossRefGoogle Scholar
  138. Peters AH et al (2001) Loss of the Suv39h histone methyltransferases impairs mammalian heterochromatin and genome stability. Cell 107:323–337PubMedCrossRefGoogle Scholar
  139. Pluta AF, Mackay AM, Ainsztein AM, Goldberg IG, Earnshaw WC (1995) The centromere: hub of chromosomal activities. Science 270:1591–1594PubMedCrossRefGoogle Scholar
  140. Pluta AF, Saitoh N, Goldberg I, Earnshaw WC (1992) Identification of a subdomain of CENP-B that is necessary and sufficient for localization to the human centromere. J Cell Biol 116:1081–1093PubMedCrossRefGoogle Scholar
  141. Przewloka MR, Venkei Z, Bolanos-Garcia VM, Debski J, Dadlez M, Glover DM (2011) CENP-C is a structural platform for kinetochore assembly Current biology : CB 21:399–405. doi: 10.1016/j.cub.2011.02.005 PubMedGoogle Scholar
  142. Quenet D, Dalal Y (2014) A long non-coding RNA is required for targeting centromeric protein A to the human centromere eLife 3:e03254. doi: 10.7554/eLife.03254 PubMedGoogle Scholar
  143. Ribeiro SA et al (2010) A super-resolution map of the vertebrate kinetochore. Proc Natl Acad Sci U S A 107:10484–10489. doi: 10.1073/pnas.1002325107 PubMedPubMedCentralCrossRefGoogle Scholar
  144. Rosic S, Kohler F, Erhardt S (2014) Repetitive centromeric satellite RNA is essential for kinetochore formation and cell division. J Cell Biol 207:335–349. doi: 10.1083/jcb.201404097 PubMedPubMedCentralCrossRefGoogle Scholar
  145. Roy B, Sanyal K (2011) Diversity in requirement of genetic and epigenetic factors for centromere function in fungi Eukaryotic. Cell 10:1384–1395. doi: 10.1128/EC.05165-11 Google Scholar
  146. Saffery R, Choo KH (2002) Strategies for engineering human chromosomes with therapeutic potential. The journal of gene medicine 4:5–13PubMedCrossRefGoogle Scholar
  147. 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 Human molecular. Genetics 9:175–185Google Scholar
  148. Santaguida S, Musacchio A (2009) The life and miracles of kinetochores. EMBO J 28:2511–2531. doi: 10.1038/emboj.2009.173 PubMedPubMedCentralCrossRefGoogle Scholar
  149. Scott KC, White CV, Willard HF (2007) An RNA polymerase III-dependent heterochromatin barrier at fission yeast centromere 1. PLoS One 2:e1099. doi: 10.1371/journal.pone.0001099 PubMedPubMedCentralCrossRefGoogle Scholar
  150. Screpanti E, De Antoni A, Alushin GM, Petrovic A, Melis T, Nogales E, Musacchio A (2011) Direct binding of Cenp-C to the Mis12 complex joins the inner and outer kinetochore. Current biology : CB 21:391–398. doi: 10.1016/j.cub.2010.12.039 PubMedPubMedCentralCrossRefGoogle Scholar
  151. Schalch T, Steiner FA (2016) Structure of centromere chromatin: from nucleosome to chromosomal architecture Chromosoma doi: 10.1007/s00412-016-0620-7
  152. Schoeftner S, Blasco MA (2010) Chromatin regulation and non-coding RNAs at mammalian telomeres Seminars in cell & developmental. Biology 21:186–193. doi: 10.1016/j.semcdb.2009.09.015 Google Scholar
  153. Schueler MG, Higgins AW, Rudd MK, Gustashaw K, Willard HF (2001) Genomic and genetic definition of a functional human centromere. Science 294:109–115. doi: 10.1126/science.1065042 PubMedCrossRefGoogle Scholar
  154. Shono N et al (2015) CENP-C and CENP-I are key connecting factors for kinetochore and CENP-A assembly. J Cell Sci 128:4572–4587. doi: 10.1242/jcs.180786 PubMedPubMedCentralCrossRefGoogle Scholar
  155. Silva MC, Bodor DL, Stellfox ME, Martins NM, Hochegger H, Foltz DR, Jansen LE (2012) Cdk activity couples epigenetic centromere inheritance to cell cycle progression Developmental. Cell 22:52–63. doi: 10.1016/j.devcel.2011.10.014 Google Scholar
  156. Slee RB et al (2012) Cancer-associated alteration of pericentromeric heterochromatin may contribute to chromosome instability. Oncogene 31:3244–3253. doi: 10.1038/onc.2011.502 PubMedCrossRefGoogle Scholar
  157. Spencer F, Gerring SL, Connelly C, Hieter P (1990) Mitotic chromosome transmission fidelity mutants in Saccharomyces cerevisiae. Genetics 124:237–249PubMedPubMedCentralGoogle Scholar
  158. Spencer F, Hieter P (1992) Centromere DNA mutations induce a mitotic delay in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 89:8908–8912PubMedPubMedCentralCrossRefGoogle Scholar
  159. Spiller F, Medina-Pritchard B, Abad MA, Wear MA, Molina O, Earnshaw WC, Jeyaprakash AA (2017) Molecular basis for Cdk1-regulated timing of Mis18 complex assembly and CENP-A deposition. EMBO Rep. doi: 10.15252/embr.201643564
  160. Stimpson KM, Matheny JE, Sullivan BA (2012) Dicentric chromosomes: unique models to study centromere function and inactivation Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome. Biology 20:595–605. doi: 10.1007/s10577-012-9302-3 Google Scholar
  161. Sugata N et al (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 11:1076–1083. doi: 10.1038/nsmb845 PubMedPubMedCentralCrossRefGoogle 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 20:227–228. doi: 10.1038/3024 PubMedCrossRefGoogle 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. Sullivan LL, Boivin CD, Mravinac B, Song IY, Sullivan BA (2011) Genomic size of CENP-A domain is proportional to total alpha satellite array size at human centromeres and expands in cancer cells Chromosome research. an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology 19:457–470. doi: 10.1007/s10577-011-9208-5 CrossRefGoogle Scholar
  167. Sumer H, Saffery R, Wong N, Craig JM, Choo KH (2004) Effects of scaffold/matrix alteration on centromeric function and gene expression. J Biol Chem 279:37631–37639. doi: 10.1074/jbc.M401051200 PubMedCrossRefGoogle Scholar
  168. Suzuki N, Nishii K, Okazaki T, Ikeno M (2006) Human artificial chromosomes constructed using the bottom-up strategy are stably maintained in mitosis and efficiently transmissible to progeny mice. J Biol Chem 281:26615–26623. doi: 10.1074/jbc.M603053200 PubMedCrossRefGoogle 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 3:819–835PubMedPubMedCentralCrossRefGoogle Scholar
  170. Takahashi K, Murakami S, Chikashige Y, Niwa O, Yanagida M (1991) A large number of tRNA genes are symmetrically located in fission yeast centromeres. J Mol Biol 218:13–17PubMedCrossRefGoogle Scholar
  171. Takiguchi M et al (2014) A novel and stable mouse artificial chromosome vector ACS. Synth Biol 3:903–914. doi: 10.1021/sb3000723 CrossRefGoogle Scholar
  172. Topp CN, Zhong CX, Dawe RK (2004) Centromere-encoded RNAs are integral components of the maize kinetochore. Proc Natl Acad Sci U S A 101:15986–15991. doi: 10.1073/pnas.0407154101 PubMedPubMedCentralCrossRefGoogle Scholar
  173. Vafa O, Sullivan KF (1997) Chromatin containing CENP-A and alpha-satellite DNA is a major component of the inner kinetochore plate. Current biology : CB 7:897–900PubMedCrossRefGoogle Scholar
  174. 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 52:1153–1163PubMedPubMedCentralGoogle Scholar
  175. Wakai M, Abe S, Kazuki Y, Oshimura M, Ishikawa F (2014) A human artificial chromosome recapitulates the metabolism of native telomeres in mammalian cells. PLoS One 9:e88530. doi: 10.1371/journal.pone.0088530 PubMedPubMedCentralCrossRefGoogle Scholar
  176. Warburton PE (2001) Epigenetic analysis of kinetochore assembly on variant human centromeres. Trends in genetics : TIG 17:243–247PubMedCrossRefGoogle Scholar
  177. Warburton PE et al (1997) Immunolocalization of CENP-A suggests a distinct nucleosome structure at the inner kinetochore plate of active centromeres. Current biology : CB 7:901–904PubMedCrossRefGoogle Scholar
  178. Waye JS, Willard HF (1989) Chromosome specificity of satellite DNAs: short- and long-range organization of a diverged dimeric subset of human alpha satellite from chromosome 3. Chromosoma 97:475–480PubMedCrossRefGoogle Scholar
  179. Willard HF (1985) Chromosome-specific organization of human alpha satellite DNA. Am J Hum Genet 37:524–532PubMedPubMedCentralGoogle Scholar
  180. Willard HF (1990) Centromeres of mammalian chromosomes. Trends in genetics : TIG 6:410–416PubMedCrossRefGoogle Scholar
  181. Yamagishi Y, Sakuno T, Shimura M, Watanabe Y (2008) Heterochromatin links to centromeric protection by recruiting shugoshin. Nature 455:251–255. doi: 10.1038/nature07217 PubMedCrossRefGoogle Scholar
  182. Young DJ, Nimmo ER, Allshire RC (1998) A Schizosaccharomyces pombe artificial chromosome large DNA cloning system. Nucleic Acids Res 26:5052–5060PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  1. 1.Wellcome Trust Centre for Cell BiologyUniversity of EdinburghEdinburghUK
  2. 2.Josep Carreras Leukaemia Research Institute. School of MedicineUniversity of BarcelonaBarcelonaSpain
  3. 3.Genome Structure and Function group, Developmental Therapeutics BranchNational Cancer Institute, National Institutes of HealthBethesdaUSA
  4. 4.Laboratory of Cell Engineering. Department of Frontier ResearchKazusa DNA Research InstituteKisarazuJapan

Personalised recommendations