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Centromere Silencing Mechanisms

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Centromeres and Kinetochores

Abstract

Centromere function is essential for genome stability and chromosome inheritance. Typically, each chromosome has a single locus that consistently serves as the site of centromere formation and kinetochore assembly. Decades of research have defined the DNA sequence and protein components of functional centromeres, and the interdependencies of specific protein complexes for proper centromere assembly. Less is known about how centromeres are disassembled or functionally silenced. Centromere silencing, or inactivation, is particularly relevant in the cases of dicentric chromosomes that occur via genome rearrangements that place two centromeres on the same chromosome. Dicentrics are usually unstable unless one centromere is inactivated, thereby allowing the structurally dicentric chromosome to behave like one of the monocentric, endogenous chromosomes. The molecular basis for centromere inactivation is not well understood, although studies in model organisms and in humans suggest that both genomic and epigenetic mechanisms are involved. In this chapter, we review recent studies using synthetic chromosomes and engineered or induced dicentrics from various organisms to define the molecular processes that are involved in the complex process of centromere inactivation.

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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 109:190–196

    Article  CAS  PubMed  Google Scholar 

  • Ahmad K, Golic KG (1998) The transmission of fragmented chromosomes in Drosophila melanogaster. Genetics 148:775–792

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bandyopadhyay R, Heller A, Knox-Dubois C, McCaskill C, Berend SA, Page SL, Shaffer LG (2002) Parental origin and timing of de novo Robertsonian translocation formation. Am J Hum Genet 71:1456–1462

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bergmann JH, Rodriguez MG, Martins NM, Kimura H, Kelly DA, Masumoto H, Larionov V, Jansen LE, Earnshaw WC (2011) Epigenetic engineering shows H3K4me2 is required for HJURP targeting and CENP-A assembly on a synthetic human kinetochore. EMBO J 30:328–340

    Article  CAS  PubMed  Google Scholar 

  • Bergmann JH, Jakubsche JN, Martins NM, Kagansky A, Nakano M, Kimura H, Kelly DA, Turner BM, Masumoto H, Larionov V, Earnshaw WC (2012) Epigenetic engineering: histone H3K9 acetylation is compatible with kinetochore structure and function. J Cell Sci 125:411

    Google Scholar 

  • Bloom K, Hill A, Jones E (1989) Conditional dicentric chromosomes in yeast. Prog Clin Biol Res 318:149–158

    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  PubMed Central  Google Scholar 

  • Bouzinba-Segard H, Guais A, Francastel C (2006) Accumulation of small murine minor satellite transcripts leads to impaired centromeric architecture and function. Proc Natl Acad Sci U S A 103:8709–8714

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cardinale S, Bergmann JH, Kelly D, Nakano M, Valdivia MM, Kimura H, Masumoto H, Larionov V, Earnshaw WC (2009) Hierarchical inactivation of a synthetic human kinetochore by a chromatin modifier. Mol Biol Cell 20:4194–4204

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Carone DM, Longo MS, Ferreri GC, Hall L, Harris M, Shook N, Bulazel KV, Carone BR, Obergfell C, O’Neill MJ, O’Neill RJ (2009) A new class of retroviral and satellite encoded small RNAs emanates from mammalian centromeres. Chromosoma 118:113–125

    Article  CAS  PubMed  Google Scholar 

  • Carone DM, Zhang C, Hall LE, Obergfell C, Carone BR, O’Neill MJ, O’Neill RJ (2013) Hypermorphic expression of centromeric retroelement-encoded small RNAs impairs CENP-A loading. Chromosome Res 21:49–62

    Article  CAS  PubMed  Google Scholar 

  • Carroll CW, Silva MC, Godek KM, Jansen LE, 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  PubMed Central  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cheeseman IM, Hori T, Fukagawa T, Desai A (2008) KNL1 and the CENP-H/I/K complex coordinately direct kinetochore assembly in vertebrates. Mol Biol Cell 19:587–594

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen CC, Bowers S, Lipinszki Z, Palladino J, Trusiak S, Bettini E, Rosin L, Przewloka MR, Glover DM, O’Neill RJ, Mellone BG (2015) Establishment of centromeric chromatin by the CENP-A assembly factor CAL1 requires FACT-mediated transcription. Dev Cell 34:73–84

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Craig JM, Earle E, Canham P, Wong LH, Anderson M, Choo KH (2003) Analysis of mammalian proteins involved in chromatin modification reveals new metaphase centromeric proteins and distinct chromosomal distribution patterns. Hum Mol Genet 12:3109–3121

    Article  CAS  PubMed  Google Scholar 

  • Daniel A (1979) Single Cd band in dicentric translocations with one suppressed centromere. Hum Genet 48:85–92

    Article  CAS  PubMed  Google Scholar 

  • de la Chapelle A, Wennstrom J, Hortling H, Ockey CH (1966) Isochromosome-X in man. I. Hereditas 54:260–276

    Article  PubMed  Google Scholar 

  • Dewald GW, Boros SJ, Conroy MM, Dahl RJ, Spurbeck JL, Vitek HA (1979) A tdic(5;15)(p31;p11) chromosome showing variation for constriction in the centromeric regions in a patient with the cri du chat syndrome. Cytogenet Cell Genet 24:15–26

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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

    Article  CAS  PubMed  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 98:1–12

    Article  CAS  PubMed  Google Scholar 

  • Eissenberg JC, Elgin SC (2014) HP1a: a structural chromosomal protein regulating transcription. Trends Genet 30:103–110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fachinetti D, Folco HD, Nechemia-Arbely Y, Valente LP, Nguyen K, Wong AJ, Zhu Q, Holland AJ, Desai A, Jansen LE, Cleveland DW (2013) A two-step mechanism for epigenetic specification of centromere identity and function. Nat Cell Biol 15:1056–1066

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Farr C, Fantes J, Goodfellow P, Cooke H (1991) Functional reintroduction of human telomeres into mammalian cells. Proc Natl Acad Sci U S A 88:7006–7010

    Article  CAS  PubMed  PubMed Central  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 LE, Bailey AO, Yates JR 3rd, 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  PubMed Central  Google Scholar 

  • Freundlieb S, Schirra-Muller C, Bujard H (1999) A tetracycline controlled activation/repression system with increased potential for gene transfer into mammalian cells. J Gene Med 1:4–12

    Article  CAS  PubMed  Google Scholar 

  • Fu S, Gao Z, Birchler J, Han F (2012) Dicentric chromosome formation and epigenetics of centromere formation in plants. J Genet Genomics 39:125–130

    Article  PubMed  Google Scholar 

  • Gascoigne KE, Cheeseman IM (2013) Induced dicentric chromosome formation promotes genomic rearrangements and tumorigenesis. Chromosome Res 21:407–418

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gascoigne KE, Takeuchi K, Suzuki A, Hori T, Fukagawa T, Cheeseman IM (2011) Induced ectopic kinetochore assembly bypasses the requirement for CENP-A nucleosomes. Cell 145:410–422

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gossen M, Freundlieb S, Bender G, Muller G, Hillen W, Bujard H (1995) Transcriptional activation by tetracyclines in mammalian cells. Science 268:1766–1769

    Article  CAS  PubMed  Google Scholar 

  • Haber JE, Thorburn PC, Rogers D (1984) Meiotic and mitotic behavior of dicentric chromosomes in Saccharomyces cerevisiae. Genetics 106:185–205

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hacein-Bey-abina S, von Kalle C, Schmidt M, McCormack MP, Wulffraat N, Leboulch P, Lim A, Osborne CS, Pawliuk R, Morillon E, Sorensen R, Forster A, Fraser P, Cohen JI, De-Saint-basile G, Alexander I, Wintergerst U, Frebourg T, Aurias A, Stoppa-Lyonnet D, Romana S, Radford-Weiss I, Gross F, Valensi F, Delabesse E, Macintyre E, Sigaux F, Soulier J, Leiva LE, Wissler M, Prinz C, Rabbitts TH, le Deist F, Fischer A, Cavazzana-Calvo M (2003) LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1. Science 302:415–419

    Article  CAS  PubMed  Google Scholar 

  • Han F, Lamb JC, Birchler JA (2006) High frequency of centromere inactivation resulting in stable dicentric chromosomes of maize. Proc Natl Acad Sci U S A 103:3238–3243

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Han F, Gao Z, Birchler JA (2009) Reactivation of an inactive centromere reveals epigenetic and structural components for centromere specification in maize. Plant Cell 21:1929–1939

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Harrington JJ, Bokkelen GV, 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

    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 

  • Higgins AW, Gustashaw KM, Willard HF (2005) Engineered human dicentric chromosomes show centromere plasticity. Chromosome Res 13:745–762

    Article  CAS  PubMed  Google Scholar 

  • Hill A, Bloom K (1987) Genetic manipulation of centromere function. Mol Cell Biol 7:2397–2405

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hill A, Bloom K (1989) Acquisition and processing of a conditional dicentric chromosome in Saccharomyces cerevisiae. Mol Cell Biol 9:1368–1370

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hill H, Golic KG (2015) Preferential breakpoints in the recovery of broken dicentric chromosomes in Drosophila melanogaster. Genetics 201:563–572

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ho KH, Tsuchiya D, Oliger AC, Lacefield S (2014) Localization and function of budding yeast CENP-A depends upon kinetochore protein interactions and is independent of canonical centromere sequence. Cell Rep 9:2027–2033

    Article  CAS  PubMed  Google Scholar 

  • Hori T, Amano M, Suzuki A, Backer CB, Welburn JP, Dong Y, McEwen BF, Shang WH, Suzuki E, Okawa K, Cheeseman IM, Fukagawa T (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 

  • Iida Y, Kim JH, Kazuki Y, Hoshiya H, Takiguchi M, Hayashi M, Erliandri I, Lee HS, Samoshkin A, Masumoto H, Earnshaw WC, Kouprina N, Larionov V, Oshimura M (2010) Human artificial chromosome with a conditional centromere for gene delivery and gene expression. DNA Res 17:293–301

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 16:431–439

    Article  CAS  PubMed  Google Scholar 

  • Izuta H, Ikeno M, Suzuki N, Tomonaga T, Nozaki N, Obuse C, Kisu Y, Goshima N, Nomura F, Nomura N, Yoda K (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 

  • Jager D, Philippsen P (1989) Stabilization of dicentric chromosomes in Saccharomyces cerevisiae by telomere addition to broken ends or by centromere deletion. EMBO J 8:247–254

    CAS  PubMed  PubMed Central  Google Scholar 

  • Janssen A, Kops GJ, Medema RH (2009) Elevating the frequency of chromosome mis-segregation as a strategy to kill tumor cells. Proc Natl Acad Sci U S A 106:19108–19113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim JH, Kononenko A, Erliandri I, Kim TA, Nakano M, Iida Y, Barrett JC, Oshimura M, Masumoto H, Earnshaw WC, Larionov V, Kouprina N (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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim JH, Lee HS, Lee NC, Goncharov NV, Kumeiko V, Masumoto H, Earnshaw WC, Kouprina N, Larionov V (2016) Development of a novel HAC-based “gain of signal” quantitative assay for measuring chromosome instability (CIN) in cancer cells. Oncotarget 7:14841–14856

    Article  PubMed  PubMed Central  Google Scholar 

  • Kononenko AV, Bansal R, Lee NC, Grimes BR, Masumoto H, Earnshaw WC, Larionov V, Kouprina N (2014) A portable BRCA1-HAC (human artificial chromosome) module for analysis of BRCA1 tumor suppressor function. Nucleic Acids Res 42:e164

    Google Scholar 

  • Kononenko AV, Lee NC, Liskovykh M, Masumoto H, Earnshaw WC, Larionov V, Kouprina N (2015) Generation of a conditionally self-eliminating HAC gene delivery vector through incorporation of a tTAVP64 expression cassette. Nucleic Acids Res 43:e57

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Koo DH, Han F, Birchler JA, Jiang J (2011) Distinct DNA methylation patterns associated with active and inactive centromeres of the maize B chromosome. Genome Res 21:908–914

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Koshland D, Rutledge L, Fitzgerald-Hayes M, Hartwell LH (1987) A genetic analysis of dicentric minichromosomes in Saccharomyces cerevisiae. Cell 48:801–812

    Article  CAS  PubMed  Google Scholar 

  • Kramer KM, Brock JA, Bloom K, Moore JK, Haber JE (1994) Two different types of double-strand breaks in Saccharomyces cerevisiae are repaired by similar RAD52-independent, nonhomologous recombination events. Mol Cell Biol 14:1293–1301

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lam AL, Boivin CD, Bonney CF, Rudd MK, Sullivan BA (2006) Human centromeric chromatin is a dynamic chromosomal domain that can spread over noncentromeric DNA. Proc Natl Acad Sci U S A 103:4186–4191

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee HS, Lee NC, Grimes BR, Samoshkin A, Kononenko AV, Bansal R, Masumoto H, Earnshaw WC, Kouprina N, Larionov V (2013) A new assay for measuring chromosome instability (CIN) and identification of drugs that elevate CIN in cancer cells. BMC Cancer 13:252

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maloney KA, Sullivan LL, Matheny JE, Strome ED, Merrett SL, Ferris A, Sullivan BA (2012) Functional epialleles at an endogenous human centromere. Proc Natl Acad Sci U S A 109:13704–13709

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mann C, Davis RW (1983) Instability of dicentric plasmids in yeast. Proc Natl Acad Sci U S A 80:228–232

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Martins NMC, 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

    Google Scholar 

  • McAinsh AD, Tytell JD, Sorger PK (2003) Structure, function, and regulation of budding yeast kinetochores. Annu Rev Cell Dev Biol 19:519–539

    Article  CAS  PubMed  Google Scholar 

  • McClintock B (1939) The behaviour of successive nuclear divisions of a chromosome broken at meiosis. Proc Natl Acad Sci U S A 25:405–416

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McClintock B (1941) The stability of broken ends of chromosomes in Zea mays. Genetics 26:234–282

    CAS  PubMed  PubMed Central  Google Scholar 

  • McKinley KL, Sekulic N, Guo LY, Tsinman T, Black BE, Cheeseman IM (2015) The CENP-L-N complex forms a critical node in an integrated meshwork of interactions at the centromere-kinetochore interface. Mol Cell 60:886–898

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mendiburo MJ, Padeken J, Fulop S, Schepers A, Heun P (2011) Drosophila CENH3 is sufficient for centromere formation. Science 334:686–690

    Article  CAS  PubMed  Google Scholar 

  • Mohebi S, Mizuno K, Watson A, Carr AM, Murray JM (2015) Checkpoints are blind to replication restart and recombination intermediates that result in gross chromosomal rearrangements. Nat Commun 6:6357

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nakano M, Okamoto Y, Ohzeki J, Masumoto H (2003) Epigenetic assembly of centromeric chromatin at ectopic alpha-satellite sites on human chromosomes. J Cell Sci 116:4021–4034

    Article  CAS  PubMed  Google Scholar 

  • 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 14:507–522

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Niebuhr E (1972) Dicentric and monocentric Robertsonian translocations in man. Humangenetik 16:217–226

    CAS  PubMed  Google Scholar 

  • Nishino T, Takeuchi K, Gascoigne KE, Suzuki A, Hori T, Oyama T, Morikawa K, Cheeseman IM, Fukagawa T (2012) CENP-T-W-S-X forms a unique centromeric chromatin structure with a histone-like fold. Cell 148:487–501

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Novitski E (1952) The genetic consequences of anaphase bridge formation in Drosophila. Genetics 37:270–287

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ockey CH, Wennstrom J, de la Chapelle A (1966) Isochromosome-X in man. II. Hereditas 54:277–292

    Article  CAS  PubMed  Google Scholar 

  • Oertel W, Mayer M (1984) Structure and mitotic stability of minichromosomes originating in yeast cells transformed with tandem dimers of CEN11 plasmids. Mol Gen Genet 195:300–307

    Article  CAS  PubMed  Google Scholar 

  • Ohzeki J, Bergmann JH, Kouprina N, Noskov VN, Nakano M, Kimura H, Earnshaw W. C, Larionov V, Masumoto H (2012) Breaking the HAC barrier: histone H3K9 acetyl/methyl balance regulates CENP-A assembly. EMBO J 31:2391

    Google Scholar 

  • Ohzeki J-I, Shono N, Otake K, Martins NMC, Kugou K, Kimura H, Nagase T, Larionov V, Earnshaw-William C, Masumoto H (2016) KAT7/HBO1/MYST2 regulates CENP-A chromatin assembly by antagonizing Suv39h1-mediated centromere inactivation. Dev Cell 37:413–427

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Olszak AM, van Essen D, Pereira AJ, Diehl S, Manke T, Maiato H, Saccani S, Heun P (2011) Heterochromatin boundaries are hotspots for de novo kinetochore formation. Nat Cell Biol 13:799–808

    Article  CAS  PubMed  Google Scholar 

  • Page SL, Earnshaw WC, Choo KH, Shaffer LG (1995) Further evidence that CENP-C is a necessary component of active centromeres: studies of a dic(X; 15) with simultaneous immunofluorescence and FISH. Hum Mol Genet 4:289–294

    Article  CAS  PubMed  Google Scholar 

  • 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 88:3734–3738

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pennaneach V, Kolodner RD (2009) Stabilization of dicentric translocations through secondary rearrangements mediated by multiple mechanisms in S. cerevisiae. PLoS One 4:e6389

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Quenet D, Dalal Y (2014) A long non-coding RNA is required for targeting centromeric protein A to the human centromere. Elife 3:e03254

    Article  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ross JE, Woodlief KS, Sullivan BA (2016) Inheritance of the CENP-A chromatin domain is spatially and temporally constrained at human centromeres. Epigenetics Chromatin 9:20

    Article  PubMed  PubMed Central  Google Scholar 

  • Saffery R, Sumer H, Hassan S, Wong LH, Craig JM, Todokoro K, Anderson M, Stafford A, Choo KHA (2003) Transcription within a functional human centromere. Mol Cell 12:509–516

    Article  CAS  PubMed  Google Scholar 

  • Saksouk N, Simboeck E, Dejardin J (2015) Constitutive heterochromatin formation and transcription in mammals. Epigenetics Chromatin 8:3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sato H, Masuda F, Takayama Y, Takahashi K, Saitoh S (2012) Epigenetic inactivation and subsequent heterochromatinization of a centromere stabilize dicentric chromosomes. Curr Biol 22:658–667

    Article  CAS  PubMed  Google Scholar 

  • Sato H, Saitoh S (2013) Switching the centromeres on and off: epigenetic chromatin alterations provide plasticity in centromere activity stabilizing aberrant dicentric chromosomes. Biochem Soc Trans 41:1648–1653

    Article  CAS  PubMed  Google Scholar 

  • Silk AD, Zasadil LM, Holland AJ, Vitre B, Cleveland DW, Weaver BA (2013) Chromosome missegregation rate predicts whether aneuploidy will promote or suppress tumors. Proc Natl Acad Sci U S A 110:4134–4141

    Article  Google Scholar 

  • Simon JA, Kingston RE (2009) Mechanisms of polycomb gene silencing: knowns and unknowns. Nat Rev Mol Cell Biol 10:697–708

    Article  CAS  PubMed  Google Scholar 

  • Stimpson KM, Song IY, Jauch A, Holtgreve-Grez H, Hayden KE, Bridger JM, Sullivan BA (2010) Telomere disruption results in non-random formation of de novo dicentric chromosomes involving acrocentric human chromosomes. PLoS Genet 6:e1001061

    Google Scholar 

  • Stimpson KM, Matheny JE, Sullivan BA (2012) Dicentric chromosomes: unique models to study centromere function and inactivation. Chromosome Res 20:595–605

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 4:2189–2197

    Article  CAS  PubMed  Google Scholar 

  • Sullivan BA, Wolff DJ, Schwartz S (1994) Analysis of centromeric activity in Robertsonian translocations: implications for a functional acrocentric hierarchy. Chromosoma 103:459–467

    Article  CAS  PubMed  Google Scholar 

  • 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 Res 19:457–470

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Suzuki A, Badger BL, Salmon ED (2015) A quantitative description of Ndc80 complex linkage to human kinetochores. Nat Commun 6:8161

    Article  PubMed  PubMed Central  Google Scholar 

  • Therman E, Trunca C, Kuhn EM, Sarto GE (1986) Dicentric chromosomes and the inactivation of the centromere. Hum Genet 72:191–195

    Article  CAS  PubMed  Google Scholar 

  • Titen SW, Golic KG (2008) Telomere loss provokes multiple pathways to apoptosis and produces genomic instability in Drosophila melanogaster. Genetics 180:1821–1832

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Volpe T, Schramke V, Hamilton GL, White SA, Teng G, Martienssen RA, Allshire RC (2003) RNA interference is required for normal centromere function in fission yeast. Chromosome Res 11:137–146

    Article  CAS  PubMed  Google Scholar 

  • 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 7:901–904

    Article  CAS  PubMed  Google Scholar 

  • Westhorpe FG, Straight AF (2013) Functions of the centromere and kinetochore in chromosome segregation. Curr Opin Cell Biol 25:334–340

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Witzgall R, O’Leary E, Leaf A, Onaldi D, Bonventre JV (1994) The Kruppel-associated box-A (KRAB-A) domain of zinc finger proteins mediates transcriptional repression. Proc Natl Acad Sci U S A 91:4514–4518

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wong LH, Brettingham-Moore KH, Chan L, Quach JM, Anderson MA, Northrop EL, Hannan R, Saffery R, Shaw ML, Williams E, Choo KH (2007) Centromere RNA is a key component for the assembly of nucleoproteins at the nucleolus and centromere. Genome Res 17:1146–1160

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang W, Friebe B, Gill BS, Jiang J (2010) Centromere inactivation and epigenetic modifications of a plant chromosome with three functional centromeres. Chromosoma 119:553–563

    Article  PubMed  Google Scholar 

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Correspondence to Beth A. Sullivan .

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McNulty, S.M., Sullivan, B.A. (2017). Centromere Silencing Mechanisms. In: Black, B. (eds) Centromeres and Kinetochores. Progress in Molecular and Subcellular Biology, vol 56. Springer, Cham. https://doi.org/10.1007/978-3-319-58592-5_10

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