Abstract
In recent years, various synthetic approaches have been developed to address the question of what directs centromere establishment and maintenance. In this chapter, we will discuss how approaches aimed at constructing synthetic centromeres have co-evolved with and contributed to shape the theory describing the determinants of centromere identity. We will first review lessons learned from artificial chromosomes created from “naked” centromeric sequences to investigate the role of the underlying DNA for centromere formation. We will then discuss how several studies, which applied removal of endogenous centromeres or over-expression of the centromere-specific histone CENP-A, helped to investigate the contribution of chromatin context to centromere establishment. Finally, we will examine various biosynthetic approaches taking advantage of targeting specific proteins to ectopic sites in the genome to dissect the role of many centromere-associated proteins and chromatin modifiers for centromere inheritance and function. Together, these studies showed that chromatin context matters, particularly proximity to heterochromatin or repetitive DNA sequences. Moreover, despite the important contribution of centromeric DNA, the centromere-specific histone H3-variant CENP-A emerges as a key epigenetic mark to establish and maintain functional centromeres on artificial chromosomes or at ectopic sites of the genome.
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References
Agudo M, Abad JP, Molina I et al (2000) A dicentric chromosome of Drosophila melanogaster showing alternate centromere inactivation. Chromosoma 109:190–196
Barnhart MC, Kuich PHJL, Stellfox ME et al (2011) HJURP is a CENP-A chromatin assembly factor sufficient to form a functional de novo kinetochore. J Cell Biol. doi:10.1083/jcb.201012017
Basu J, Stromberg G, Compitello G et al (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
Bergmann JH, Jakubsche JN, Martins NM et al (2012) Epigenetic engineering: histone H3K9 acetylation is compatible with kinetochore structure and function. J Cell Sci 125:411–421. doi:10.1242/jcs.090639
Bergmann JH, Rodriguez MG, Martins NMC 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
Bernard P, Maure JF, Partridge JF et al (2001) Requirement of heterochromatin for cohesion at centromeres. Science 294:2539–2542. doi:10.1126/science.1064027
Black BE, Jansen LET, Maddox PS et al (2007) centromere identity maintained by nucleosomes assembled with histone H3 containing the CENP-A targeting domain. Mol Cell. doi:10.1016/j.molcel.2006.12.018
Blower MD, Karpen GH (2001) The role of Drosophila CID in kinetochore formation, cell-cycle progression and heterochromatin interactions. Nat Cell Biol 3:730–739. doi:10.1038/35087045
Blower MD, Sullivan BA, Karpen GH (2002) Conserved organization of centromeric chromatin in flies and humans. Dev Cell 2:319–330
Cardinale S, Bergmann JH, Kelly D 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
Castillo AG, Pidoux AL, Catania S et al (2013) Telomeric repeats facilitate CENP-ACnp1 Incorporation via telomere binding proteins. PLoS ONE. doi:10.1371/journal.pone.0069673
Chen C-C, Dechassa ML, Bettini E et al (2014) CAL1 is the Drosophila CENP-A assembly factor. J Cell Biol 204:313–329. doi:10.1083/jcb.201305036
Chen CC, Bowers S, Lipinszki Z et al (2015) Establishment of centromeric chromatin by the CENP-A assembly factor CAL1 requires FACT-mediated transcription. Dev Cell. doi:10.1016/j.devcel.2015.05.012
Clarke L, Carbon J (1980) Isolation of a yeast centromere and construction of functional small circular chromosomes. Nature 287:504–509
Earnshaw WC, Migeon BR (1985) Three related centromere proteins are absent from the inactive centromere of a stable isodicentric chromosome. Chromosoma 92:290–296
Ebersole T, Okamoto Y, Noskov VN 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
Fachinetti D, Folco HD, Nechemia-Arbely Y 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
Fachinetti D, Logsdon GA, Abdullah A et al (2017) CENP-A modifications on ser68 and Lys124 are dispensable for establishment, maintenance, and long-term function of human centromeres. Dev Cell 40:104–113. doi:10.1016/j.devcel.2016.12.014
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
Foltz DR, Jansen LET, Bailey AO et al (2009) Centromere-specific assembly of CENP-A nucleosomes Is mediated by HJURP. Cell. doi:10.1016/j.cell.2009.02.039
Fujita Y, Hayashi T, Kiyomitsu T et al (2007) Priming of centromere for CENP-A recruitment by human hMis18, hMis18, and M18BP1. Dev Cell. doi:10.1016/j.devcel.2006.11.002
Gascoigne KE, Takeuchi K, Suzuki A et al (2011) Induced ectopic kinetochore assembly bypasses the requirement for CENP-A nucleosomes. Cell. doi:10.1016/j.cell.2011.03.031
Guse A, Carroll CW, Moree B et al (2011) In vitro centromere and kinetochore assembly on defined chromatin templates. Nature 477:354–358. doi:10.1038/nature10379
Hahnenberger KM, Baum MP, Polizzi CM et al (1989) Construction of functional artificial minichromosomes in the fission yeast Schizosaccharomyces pombe. Proc Natl Acad Sci U S A 86:577–581
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. doi:10.1073/pnas.0509650103
Harrington JJ, Van Bokkelen G, Mays RW et al (1997) Formation of de novo centromeres and construction of first-generation human artificial microchromosomes. Nat Genet 15:345–355. doi:10.1038/ng0497-345
Hassold T, Hunt P (2001) To err (meiotically) is human: the genesis of human aneuploidy. Nat Rev Genet 2:280–291. doi:10.1038/35066065
Hayashi T, Fujita Y, Iwasaki O et al (2004) Mis16 and Mis18 are required for CENP-A loading and histone deacetylation at centromeres. Cell. doi:10.1016/j.cell.2004.09.002
Heun P, Erhardt S, Blower MD et al (2006) Mislocalization of the drosophila centromere-specific histone CID promotes formation of functional ectopic kinetochores. Dev Cell. doi:10.1016/j.devcel.2006.01.014
Hill A, Bloom K (1989) Acquisition and processing of a conditional dicentric chromosome in Saccharomyces cerevisiae. Mol Cell Biol 9:1368–1370
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. doi:10.1083/jcb.201210106
Hudson DF, Fowler KJ, Earle E et al (1998) Centromere protein B null mice are mitotically and meiotically normal but have lower body and testis weights. J Cell Biol 141:309–319
Ikeno M, Grimes B, Okazaki T et al (1998) Construction of YAC-based mammalian artificial chromosomes. Nat Biotechnol 16:431–439. doi:10.1038/nbt0598-431
Ishii K, Ogiyama Y, Chikashige Y et al (2008) Heterochromatin integrity affects chromosome reorganization after centromere dysfunction. Science 321:1088–1091. doi:10.1126/science.1158699
Kagansky A, Folco HD, Almeida R et al (2009) Synthetic heterochromatin bypasses RNAi and centromeric repeats to establish functional centromeres. Science 324:1716–1719. doi:10.1126/science.1172026
Kapoor M, de Montes Oca Luna R, Liu G et al (1998) The cenpB gene is not essential in mice. Chromosoma 107:570–576
Karpen GH, Allshire RC (1997) The case for epigenetic effects on centromere identity and function. Trends Genet 13:489–496
Ketel C, Wang HSW, McClellan M et al (2009) Neocentromeres form efficiently at multiple possible loci in Candida albicans. PLoS Genet 5:e1000400. doi:10.1371/journal.pgen.1000400
Logsdon GA, Barrey EJ, Bassett EA et al (2015) Both tails and the centromere targeting domain of CENP-A are required for centromere establishment. J Cell Biol. doi:10.1083/jcb.201412011
Maggert KA, Karpen GH (2001) The activation of a neocentromere in Drosophila requires proximity to an endogenous centromere. Genetics 158:1615–1628
Marshall OJ, Chueh AC, Wong LH, Choo KHA (2008) Neocentromeres: new insights into centromere structure, disease development, and karyotype evolution. Am. J. Hum, Genet
Martins NMC, Bergmann JH, Shono N et al (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
Masumoto H, Ikeno M, Nakano M et al (1998) Assay of centromere function using a human artificial chromosome. Chromosoma 107:406–416
Mendiburo MJ, Padeken J, Fulop S et al (2011) Drosophila CENH3 is sufficient for centromere formation. Science 334:686–690. doi:10.1126/science.1206880
Murray AW, Szostak JW (1983) Construction of artificial chromosomes in yeast. Nature 305:189–193
Nakano M, Cardinale S, Noskov VN et al (2008) Inactivation of a human kinetochore by specific targeting of chromatin modifiers. Dev Cell. doi:10.1016/j.devcel.2008.02.001
Niikura Y, Kitagawa R, Kitagawa K (2016) CENP-A ubiquitylation is inherited through dimerization between cell divisions. Cell Rep 15:61–76. doi:10.1016/j.celrep.2016.03.010
Nonaka N, Kitajima T, Yokobayashi S et al (2002) Recruitment of cohesin to heterochromatic regions by Swi6/HP1 in fission yeast. Nat Cell Biol 4:89–93. doi:10.1038/ncb739
Ohzeki J-I, Bergmann JH, Kouprina N et al (2012) Breaking the HAC barrier: histone H3K9 acetyl/ methyl balance regulates CENP-A assembly. EMBO J 3182:2391–2402. doi:10.1038/emboj.2012.82
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. doi:10.1083/jcb.200207112
Okada T, Ohzeki J, Nakano M et al (2007) CENP-B controls centromere formation depending on the chromatin context. Cell. doi:10.1016/j.cell.2007.10.045
Okamoto Y, Nakano M, Ohzeki J et al (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
Olszak AM, van Essen D, Pereira AJ et al (2011) Heterochromatin boundaries are hotspots for de novo kinetochore formation. Nat Cell Biol 13:799–808. doi:10.1038/ncb2272
Perez-Castro AV, Shamanski FL, Meneses JJ et al (1998) Centromeric protein B null mice are viable with no apparent abnormalities. Dev Biol 201:135–143. doi:10.1006/dbio.1998.9005
Robinett CC, Straight A, Li G et al (1996) In vivo localization of DNA sequences and visualization of large-scale chromatin organization using lac operator/repressor recognition. J Cell Biol 135:1685–1700
Schueler MG, Sullivan BA (2006) Structural and functional dynamics of human centromeric chromatin. Annu Rev Genomics Hum Genet 7:301–313. doi:10.1146/annurev.genom.7.080505.115613
Shang WH, Hori T, Martins NMC et al (2013) Chromosome engineering allows the efficient isolation of vertebrate neocentromeres. Dev Cell. doi:10.1016/j.devcel.2013.02.009
Shono N, Ohzeki J, Otake K 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
Stellfox ME, Nardi IK, Knippler CM, Foltz DR (2016) Differential binding partners of the Mis18α/β YIPPEE domains regulate Mis18 complex recruitment to centromeres. Cell Rep. doi:10.1016/j.celrep.2016.05.004
Stimpson KM, Matheny JE, Sullivan BA (2012) Dicentric chromosomes: unique models to study centromere function and inactivation. Chromosom Res 20:595–605. doi:10.1007/s10577-012-9302-3
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
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
Tachiwana H, Müller S, Blümer J et al (2015) HJURP involvement in de novo CenH3CENP-A and CENP-C recruitment. Cell Rep. doi:10.1016/j.celrep.2015.03.013
Van Hooser AA, Ouspenski II, Gregson HC et al (2001) Specification of kinetochore-forming chromatin by the histone H3 variant CENP-A. J Cell Sci 114:3529–3542
Weaver BAA, Cleveland DW (2007) Aneuploidy: instigator and inhibitor of tumorigenesis. Cancer Res 67:10103–10105. doi:10.1158/0008-5472.CAN-07-2266
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Barrey, E.J., Heun, P. (2017). Artificial Chromosomes and Strategies to Initiate Epigenetic Centromere Establishment. 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_8
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