Skip to main content
Log in

CENP-A regulates chromosome segregation during the first meiosis of mouse oocytes

  • Original Article
  • Published:
Journal of Huazhong University of Science and Technology [Medical Sciences] Aims and scope Submit manuscript

Summary

Proper chromosome separation in both mitosis and meiosis depends on the correct connection between kinetochores of chromosomes and spindle microtubules. Kinetochore dysfunction can lead to unequal distribution of chromosomes during cell division and result in aneuploidy, thus kinetochores are critical for faithful segregation of chromosomes. Centromere protein A (CENP-A) is an important component of the inner kinetochore plate. Multiple studies in mitosis have found that deficiencies in CENP-A could result in structural and functional changes of kinetochores, leading to abnormal chromosome segregation, aneuploidy and apoptosis in cells. Here we report the expression and function of CENP-A during mouse oocyte meiosis. Our study found that microinjection of CENP-A blocking antibody resulted in errors of homologous chromosome segregation and caused aneuploidy in eggs. Thus, our findings provide evidence that CENP-A is critical for the faithful chromosome segregation during mammalian oocyte meiosis.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Akiyoshi B, Biggins S. Reconstituting the kinetochore-microtubule interface: what, why, and how. Chromosoma, 2012,121(3):235–250

    Article  PubMed  PubMed Central  Google Scholar 

  2. Brar GA, Amon A. Emerging roles for centromeres in meiosis I chromosome segregation. Nat Rev Genet, 2008, 9(12):899–910

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Verdaasdonk JS, Bloom K. Centromeres: unique chromatin structures that drive chromosome segregation. Nat Rev Mol Cell Biol, 2011,12(5):320–332

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Akiyoshi B, Biggins S. Reconstituting the kinetochore-microtubule interface: what, why, and how. Chromosoma, 2012,121(3):235–250

    Article  PubMed  PubMed Central  Google Scholar 

  5. Simerly C, Balczon R, Brinkley B R, et al. Microinjected kinetochore antibodies interfere with chromosome movement in meiotic and mitotic mouse oocytes. J Cell Biol, 1990,111(4):1491–1504

    Article  CAS  PubMed  Google Scholar 

  6. Watanabe Y. Geometry and force behind kinetochore orientation: lessons from meiosis. Nat Rev Mol Cell Biol, 2012,13(6):370–382

    Article  CAS  PubMed  Google Scholar 

  7. Durand-Dubief M, Ekwall K. Heterochromatin tells CENP-A where to go. Bioessays, 2008,30(6):526–529

    Article  CAS  PubMed  Google Scholar 

  8. Sullivan KF, Hechenberger M, Masri K. Human CENP-A contains a histone H3 related histone fold domain that is required for targeting to the centromere. J Cell Biol, 1994,127(3):581–592

    Article  CAS  PubMed  Google Scholar 

  9. Mendiburo MJ, Padeken J, Fulop S, et al. Drosophila CENH3 is sufficient for centromere formation. Science, 2011,334(6056):686–690

    Article  CAS  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  11. Zhang W, Colmenares SU, Karpen GH. Assembly of Drosophila centromeric nucleosomes requires CID dimerization. Mol Cell, 2012,45(2):263–269

    Article  CAS  PubMed  Google Scholar 

  12. Figueroa J, Saffrich R, Ansorge W, et al. Microinjection of antibodies to centromere protein CENP-A arrests cells in interphase but does not prevent mitosis. Chromosoma, 1998,107(6–7):397–405

    Article  CAS  PubMed  Google Scholar 

  13. Goshima G, Kiyomitsu T, Yoda K, et al. Human centromere chromatin protein hMis12, essential for equal segregation, is independent of CENP-A loading pathway. J Cell Biol, 2003,160(1):25–39

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Howman EV, Fowler KJ, Newson AJ, et al. Early disruption of centromeric chromatin organization in centromere protein A (Cenpa) null mice. Proc Natl Acad Sci USA, 2000,97(3):1148–1153

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Monen J, Maddox PS, Hyndman F, et al. Differential role of CENP-A in the segregation of holocentric C. elegans chromosomes during meiosis and mitosis. Nat Cell Biol, 2005,7(12):1248–1255

    PubMed  Google Scholar 

  16. Raychaudhuri N, Dubruille R, Orsi GA, et al. Transgenerational propagation and quantitative maintenance of paternal centromeres depends on Cid/Cenp-A presence in Drosophila sperm. PLoS Biol, 2012,10(12):e1001434

    Article  Google Scholar 

  17. Dunleavy EM, Beier NL, Gorgescu W, et al. The cell cycle timing of centromeric chromatin assembly in Drosophila meiosis is distinct from mitosis yet requires CAL1 and CENP-C. PLoS Biol, 2012,10(12):e1001460

    Article  Google Scholar 

  18. Qi ST, Wang ZB, Ouyang YC, et al. Overexpression of SETbeta, a protein localizing to centromeres, causes precocious separation of chromatids during the first meiosis of mouse oocytes. J Cell Sci, 2013,126(Pt 7): 1595–1603

    Article  CAS  PubMed  Google Scholar 

  19. Luo YB, Ma JY, Zhang QH, et al. MBTD1 is associated with Pr-Set7 to stabilize H4K20me1 in mouse oocyte meiotic maturation. Cell Cycle, 2013,12(7):1142–1150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Shelby RD, Monier K, Sullivan KF. Chromatin assembly at kinetochores is uncoupled from DNA replication. J Cell Biol, 2000,151(5):1113–1118

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Shelby RD, Vafa O, Sullivan KF. Assembly of CENP-A into centromeric chromatin requires a cooperative array of nucleosomal DNA contact sites. J Cell Biol, 1997, 136(3):501–513

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Bodor DL, Valente LP, Mata JF, et al. Assembly in G1 phase and long-term stability are unique intrinsic features of CENP-A nucleosomes. Mol Biol Cell, 2013,24(7):923–932

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Kim IS, Lee M, Park KC, et al. Roles of Mis18alpha in epigenetic regulation of centromeric chromatin and CENP-A loading. Mol Cell, 2012,46(3):260–273

    Article  CAS  PubMed  Google Scholar 

  24. Bui M, Dimitriadis EK, Hoischen C, et al. Cell-cycle-dependent structural transitions in the human CENP-A nucleosome in vivo. Cell, 2012,150(2):317–326

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Tachiwana H, Kagawa W, Shiga T, et al. Crystal structure of the human centromeric nucleosome containing CENP-A. Nature, 2011,476(7359):232–235

    Article  CAS  PubMed  Google Scholar 

  26. Ranjitkar P, Press MO, Yi X, et al. An E3 ubiquitin ligase prevents ectopic localization of the centromeric histone H3 variant via the centromere targeting domain. Mol Cell, 2010,40(3):455–464

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Hewawasam G, Shivaraju M, Mattingly M, et al. Psh1 is an E3 ubiquitin ligase that targets the centromeric histone variant Cse4. Mol Cell, 2010,40(3):444–454

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Moreno-Moreno O, Medina-Giro S, Torras-Llort M, et al. The F box protein partner of paired regulates stability of Drosophila centromeric histone H3, CenH3(CID). Curr Biol, 2011,21(17):1488–1493

    Article  CAS  PubMed  Google Scholar 

  29. Sekulic N, Bassett EA, Rogers DJ, et al. The structure of (CENP-A-H4)(2) reveals physical features that mark centromeres. Nature, 2010, 467(7313):347–351

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Carroll CW, Milks KJ, Straight AF. Dual recognition of CENP-A nucleosomes is required for centromere assembly. J Cell Biol, 2010,189(7):1143–1155

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Black BE, Brock MA, Bedard S, et al. An epigenetic mark generated by the incorporation of CENP-A into centromeric nucleosomes. Proc Natl Acad Sci USA, 2007,104(12):5008–5013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Chiang T, Duncan FE, Schindler K, et al. Evidence that weakened centromere cohesion is a leading cause of age-related aneuploidy in oocytes. Curr Biol, 2010,20(17):1522–1528

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank Shi-wen LI and Hua QIN for their technical help with confocal laser microscopy. We also thank the other members in Dr. Sun’s laboratory for their kind discussions and help.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Shi-ling Chen  (陈士岭).

Additional information

This study was supported by the National Natural Science Foundation of China (No. 30930065 and No. 31271605).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, L., Qi, St., Sun, Qy. et al. CENP-A regulates chromosome segregation during the first meiosis of mouse oocytes. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 37, 313–318 (2017). https://doi.org/10.1007/s11596-017-1733-9

Download citation

  • Received:

  • Revised:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11596-017-1733-9

Key words

Navigation