Skip to main content

Centromere Dynamics in Male and Female Germ Cells

  • Chapter
  • First Online:
Centromeres and Kinetochores

Part of the book series: Progress in Molecular and Subcellular Biology ((PMSB,volume 56))

Abstract

In sexually reproducing organisms the germ line is the cellular lineage that gives rise to gametes. All germ cells originate from germline stem cells that divide asymmetrically to generate gonial pre-cursors, which are amplified in number by mitotic divisions, undergo meiosis and eventually differentiate into mature gametes (haploid eggs and sperm). Information transmitted with gametes is inherited by offspring, and potentially by subsequent generations, instructing in organismal development and beyond. Meiosis comprises one round of DNA replication, followed by two rounds of chromosome segregation; homologous chromosomes segregate in the first division (meiosis I) and sister chromatids segregate in the second division (meiosis II). Important mechanistic features of meiosis occur in substages of prophase I and are critical for genetic recombination, including pairing and synapsis of homologous chromosomes (at leptotene and zygotene), crossing-over (at pachytene), and the appearance of chiasmata (at diplotene/diakinesis). Another unique feature of meiosis is the altered centromere/kinetochore geometry at metaphase I, such that sister kinetochores face the same spindle pole (mono-orientation) and stay together at anaphase I. This chapter reviews centromere dynamics in germ cells, focusing on centromere function and assembly in meiotic cell cycles, as well as centromere inheritance in zygotes. Centromeres are functionally defined by the presence of the histone H3 variant CENP-A, the epigenetic determinant of centromere identity. In most eukaryotes, it is well established that CENP-A function is essential for chromosome segregation in mitosis. CENP-A function in meiosis is less well understood and emerging insights into the differential regulation of meiotic and mitotic CENP-A are discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Black BE, Foltz DR, Chakravarthy S, Luger K, Woods VL, Cleveland DW (2004) Structural determinants for generating centromeric chromatin. Nature 430:578–582

    Article  CAS  PubMed  Google Scholar 

  • Black BE, Jansen LE, Maddox PS, Foltz DR, Desai AB, Shah JV, Cleveland DW (2007) 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, Karpen GH (2001) The role of Drosophila CID in kinetochore formation, cell-cycle progression and heterochromatin interactions. Nat Cell Biol 3:730–739

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Buchwitz BJ, Ahmad K, Moore LL, Roth MB, Henikoff S (1999) A histone-H3-like protein in C. elegans. Nature 401:547–548

    Article  CAS  PubMed  Google Scholar 

  • Cahoon CK, Hawley RS (2016) Regulating the construction and demolition of the synaptonemal complex. Nat Struct Mol Biol 23:369–377

    Article  PubMed  Google Scholar 

  • Carroll CW, Milks KJ, Straight AF (2010) Dual recognition of CENP-A nucleosomes is required for centromere assembly. J Cell Biol 189:1143–1155

    Article  CAS  PubMed  PubMed Central  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 

  • Chan FL, Wong LH (2012) Transcription in the maintenance of centromere chromatin identity. Nucleic Acids Res 40:11178–11188

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Christophorou N, Rubin T, Huynh JR (2013) Synaptonemal complex components promote centromere pairing in pre-meiotic germ cells. PLoS Genet 9:e1004012

    Article  PubMed  PubMed Central  Google Scholar 

  • Dereeper A, Audic S, Claverie JM, Blanc G (2010) BLAST-EXPLORER helps you building datasets for phylogenetic analysis. BMC Evol Biol 10:18

    Article  Google Scholar 

  • Dumont J, Oegema K, Desai A (2010) A kinetochore-independent mechanism drives anaphase chromosome separation during acentrosomal meiosis. Nat Cell Biol 12:894–901

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dunleavy EM, Beier NL, Gorgescu W, Tang J, Costes SV, Karpen GH (2012) The cell cycle timing of centromeric chromatin assembly in Drosophila meiosis is distinct from mitosis yet requires CAL1 and CENP-C. PLoS Biol 10:e1001460

    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 

  • Falk SJ, Guo LY, Sekulic N, Smoak EM, Mani T, Logsdon GA, Gupta K, Jansen LE, van Duyne GD, Vinogradov SA, Lampson MA, Black BE (2015) Chromosomes. CENP-C reshapes and stabilizes CENP-A nucleosomes at the centromere. Science 348:699–703

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Gassmann R, Rechtsteiner A, Yuen KW, Muroyama A, Egelhofer T, Gaydos L, Barron F, Maddox P, Essex A, Monen J, Ercan S, Lieb JD, Oegema K, Strome S, Desai A (2012) An inverse relationship to germline transcription defines centromeric chromatin in C. elegans. Nature 484:534–537

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Heeger S, Leismann O, Schittenhelm R, Schraidt O, Heidmann S, Lehner CF (2005) Genetic interactions of separase regulatory subunits reveal the diverged Drosophila Cenp-C homolog. Genes Dev 19:2041–2053

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hemmerich P, Weidtkamp-Peters S, Hoischen C, Schmiedeberg L, Erliandri I, Diekmann S (2008) Dynamics of inner kinetochore assembly and maintenance in living cells. J Cell Biol 180:1101–1114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Howman EV, Fowler KJ, Newson AJ, Redward S, Macdonald AC, Kalitsis P, Choo KH (2000) Early disruption of centromeric chromatin organization in centromere protein A (Cenpa) null mice. Proc Natl Acad Sci U S A 97:1148–1153

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ingouff M, Rademacher S, Holec S, Soljić L, Xin N, Readshaw A, Foo SH, Lahouze B, Sprunck S, Berger F (2010) Zygotic resetting of the HISTONE 3 variant repertoire participates in epigenetic reprogramming in Arabidopsis. Curr Biol 20:2137–2143

    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  PubMed Central  Google Scholar 

  • Kalitsis P, Fowler KJ, Earle E, Hill J, Choo KH (1998) Targeted disruption of mouse centromere protein C gene leads to mitotic disarray and early embryo death. Proc Natl Acad Sci U S A 95:1136–1141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Karimi-Ashtiyani R, Ishii T, Niessen M, Stein N, Heckmann S, Gurushidze M, Banaei-Moghaddam AM, Fuchs J, Schubert V, Koch K, Weiss O, Demidov D, Schmidt K, Kumlehn J, Houben A (2015) Point mutation impairs centromeric CENH3 loading and induces haploid plants. Proc Natl Acad Sci U S A 112:11211–11216

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim J, Ishiguro K, Nambu A, Akiyoshi B, Yokobayashi S, Kagami A, Ishiguro T, Pendas AM, Takeda N, Sakakibara Y, Kitajima TS, Tanno Y, Sakuno T, Watanabe Y (2015) Meikin is a conserved regulator of meiosis-I-specific kinetochore function. Nature 517:466–471

    Article  CAS  PubMed  Google Scholar 

  • Kwenda L, Collins CM, Dattoli AA, Dunleavy EM (2016) Nucleolar activity and CENP-C regulate CENP-A and CAL1 availability for centromere assembly in meiosis. Development 143:1400–1412

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lando D, Endesfelder U, Berger H, Subramanian L, Dunne PD, McColl J, Klenerman D, Carr AM, Sauer M, Allshire RC, Heilemann M, Laue ED (2012) Quantitative single-molecule microscopy reveals that CENP-A(Cnp1) deposition occurs during G2 in fission yeast. Open Biol 2:120078

    Article  PubMed  PubMed Central  Google Scholar 

  • Lermontova I, Fuchs J, Schubert V, Schubert I (2007) Loading time of the centromeric histone H3 variant differs between plants and animals. Chromosoma 116:507–510

    Article  PubMed  Google Scholar 

  • Lermontova I, Koroleva O, Rutten T, Fuchs J, Schubert V, Moraes I, Koszegi D, Schubert I (2011) Knockdown of CENH3 in Arabidopsis reduces mitotic divisions and causes sterility by disturbed meiotic chromosome segregation. Plant J 68:40–50

    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  PubMed Central  Google Scholar 

  • Logsdon GA, Barrey EJ, Bassett EA, Denizio JE, Guo LY, Panchenko T, Dawicki-Mckenna JM, Heun P, Black BE (2015) Both tails and the centromere targeting domain of CENP-A are required for centromere establishment. J Cell Biol 208:521–531

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maheshwari S, Tan EH, West A, Franklin FC, Comai L, Chan SW (2015) Naturally occurring differences in CENH3 affect chromosome segregation in zygotic mitosis of hybrids. PLoS Genet 11:e1004970

    Article  PubMed  PubMed Central  Google Scholar 

  • Malik HS, Henikoff S (2003) Phylogenomics of the nucleosome. Nat Struct Biol 10:882–891

    Article  CAS  PubMed  Google Scholar 

  • Malik HS, Vermaak D, Henikoff S (2002) Recurrent evolution of DNA-binding motifs in the Drosophila centromeric histone. Proc Natl Acad Sci U S A 99:1449–1454

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marques A, Pedrosa-Harand A (2016) Holocentromere identity: from the typical mitotic linear structure to the great plasticity of meiotic holocentromeres. Chromosoma 125(4):669–81

    Google Scholar 

  • Meluh PB, Koshland D (1995) Evidence that the MIF2 gene of Saccharomyces cerevisiae encodes a centromere protein with homology to the mammalian centromere protein CENP-C. Mol Biol Cell 6:793–807

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Meyer GF (1960) Proceedings of the European regional conference on electron microscopy. Die Nederlandse Verening voor Electronmicroscopic Delft

    Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Monen J, Maddox PS, Hyndman F, Oegema K, Desai A (2005) Differential role of CENP-A in the segregation of holocentric C. elegans chromosomes during meiosis and mitosis. Nat Cell Biol 7:1248–1255

    Article  PubMed  Google Scholar 

  • Notredame C, Higgins DG, Heringa J (2000) T-Coffee: a novel method for fast and accurate multiple sequence alignment. J Mol Biol 302:205–217

    Article  CAS  PubMed  Google Scholar 

  • Palmer DK, O’Day K, Margolis RL (1990) The centromere specific histone CENP-A is selectively retained in discrete foci in mammalian sperm nuclei. Chromosoma 100:32–36

    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 

  • Ravi M, Chan SW (2010) Haploid plants produced by centromere-mediated genome elimination. Nature 464:615–618

    Article  CAS  PubMed  Google Scholar 

  • Ravi M, Kwong PN, Menorca RM, Valencia JT, Ramahi JS, Stewart JL, Tran RK, Sundaresan V, Comai L, Chan SW (2010) The rapidly evolving centromere-specific histone has stringent functional requirements in Arabidopsis thaliana. Genetics 186:461–471

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ravi M, Shibata F, Ramahi JS, Nagaki K, Chen C, Murata M, Chan SW (2011) Meiosis-specific loading of the centromere-specific histone CENH3 in Arabidopsis thaliana. PLoS Genet 7:e1002121

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Raychaudhuri N, Dubruille R, Orsi GA, Bagheri HC, Loppin B, Lehner CF (2012) Transgenerational propagation and quantitative maintenance of paternal centromeres depends on Cid/Cenp-A presence in Drosophila sperm. PLoS Biol 10:e1001434

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sanei M, Pickering R, Kumke K, Nasuda S, Houben A (2011) Loss of centromeric histone H3 (CENH3) from centromeres precedes uniparental chromosome elimination in interspecific barley hybrids. Proc Natl Acad Sci U S A 108:E498–E505

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schittenhelm RB, Althoff F, Heidmann S, Lehner CF (2010) Detrimental incorporation of excess Cenp-A/Cid and Cenp-C into Drosophila centromeres is prevented by limiting amounts of the bridging factor Cal1. J Cell Sci 123:3768–3779

    Article  CAS  PubMed  Google Scholar 

  • Schubert V, Lermontova I, Schubert I (2014) Loading of the centromeric histone H3 variant during meiosis-how does it differ from mitosis? Chromosoma 123:491–497

    Article  CAS  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 

  • 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. Dev Cell 22:52–63

    Article  CAS  PubMed  Google Scholar 

  • Smoak EM, Stein P, Schultz RM, Lampson MA, Black BE (2016) Long-term retention of CENP-A nucleosomes in Mammalian oocytes underpins transgenerational inheritance of centromere identity. Curr Biol 26:1110–1116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stoler S, Keith KC, Curnick KE, Fitzgerald-Hayes M (1995) A mutation in CSE4, an essential gene encoding a novel chromatin-associated protein in yeast, causes chromosome nondisjunction and cell cycle arrest at mitosis. Genes Dev 9:573–586

    Article  CAS  PubMed  Google Scholar 

  • Takahashi K, Chen ES, Yanagida M (2000) Requirement of Mis6 centromere connector for localizing a CENP-A-like protein in fission yeast. Science 288:2215–2219

    Article  CAS  PubMed  Google Scholar 

  • Takeo S, Lake CM, Morais-De-sĂ¡ E, Sunkel CE, Hawley RS (2011) Synaptonemal complex-dependent centromeric clustering and the initiation of synapsis in Drosophila oocytes. Curr Biol 21:1845–1851

    Article  CAS  PubMed  Google Scholar 

  • Tanaka K, Chang HL, Kagami A, Watanabe Y (2009) CENP-C functions as a scaffold for effectors with essential kinetochore functions in mitosis and meiosis. Dev Cell 17:334–343

    Article  PubMed  Google Scholar 

  • Tanneti NS, Landy K, Joyce EF, McKim KS (2011) A pathway for synapsis initiation during zygotene in Drosophila oocytes. Curr Biol 21:1852–1857

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tsubouchi T, Macqueen AJ, Roeder GS (2008) Initiation of meiotic chromosome synapsis at centromeres in budding yeast. Genes Dev 22:3217–3226

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Unhavaithaya Y, Orr-Weaver TL (2013) Centromere proteins CENP-C and CAL1 functionally interact in meiosis for centromere clustering, pairing, and chromosome segregation. Proc Natl Acad Sci U S A 110:19878–19883

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Valente LP, Silva MC, Jansen LE (2012) Temporal control of epigenetic centromere specification. Chromosome Res 20:481–492

    Article  CAS  PubMed  Google Scholar 

  • von Stetina JR, Orr-Weaver TL (2011) Developmental control of oocyte maturation and egg activation in metazoan models. Cold Spring Harb Perspect Biol 3:a005553

    Google Scholar 

  • Watanabe Y (2012) Geometry and force behind kinetochore orientation: lessons from meiosis. Nat Rev Mol Cell Biol 13:370–382

    Article  CAS  PubMed  Google Scholar 

  • Zeitlin SG, Patel S, Kavli B, Slupphaug G (2005) Xenopus CENP-A assembly into chromatin requires base excision repair proteins. DNA Repair (Amst) 4:760–772

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Elaine M. Dunleavy .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Dunleavy, E.M., Collins, C.M. (2017). Centromere Dynamics in Male and Female Germ Cells. 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_15

Download citation

Publish with us

Policies and ethics