Science China Life Sciences

, Volume 62, Issue 6, pp 829–837 | Cite as

Characterization of H3 methylation in regulating oocyte development in cyprinid fish

  • Rong Zhou
  • Rujie Shang
  • Dingbin Gong
  • Xiujuan Xu
  • Shaojun LiuEmail author
Research Paper


Histone post-modifications are important epigenetic markers involved in multiple cellular processes via regulation of gene transcription or remodeling of chromatin structure. Oocyte development is a critical process under rigorous control to prevent the generation of aberrant gametes. However, the regulatory mechanism of oocyte early development is not well-understood due to the tiny size and poor distinguishability of the gonad in juvenile stages. Here, two cyprinid hybrid fishes, a sterile allotriploid fish and a gynogenetic hybrid fish with delayed oocyte development, provided research models to investigate the mechanisms involved. We used cytogenetic and molecular methods to confirm the pachytene arrest of oocytes in allotriploid fish and gynogenetic hybrid fish. On the basis of these developmental differences, we screened 21 different histone H3 modifications by ELISA and found that four modifications (H3K4me3, H3K9me3, H3K79me, and H3K79me3) differed significantly in the two cyprinid hybrid fishes. Changes in histone methylation at the three residues (H3K4, K9, K79) were caused by specific methyltransferases and demethylases. Our results provide new insights into the epigenetic regulation of oocyte early development in fish, a process critical for understanding of reproductive biology and with practical applications in the aquacultural breeding industry.


histone methylation oocyte development sterility allotriploid fish 


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This work was supported by the National Natural Science Foundation of China (31402297, 31730098), the earmarked fund for China Agriculture Research System (CARS-45), the Natural Science Foundation of Hunan Province (2018JJ3338).

Supplementary material

11427_2018_9346_MOESM1_ESM.doc (68 kb)
TABLE S1 Nucleotide sequences and positions of primers used in PCR.


  1. Baarends, W.M., and Grootegoed, J.A. (2003). Chromatin dynamics in the male meiotic prophase. Cytogenet Genome Res 103, 225–234.CrossRefGoogle Scholar
  2. Baudat, F., Buard, J., Grey, C., Fledel-Alon, A., Ober, C., Przeworski, M., Coop, G., and de Massy, B. (2010). PRDM9 is a major determinant of meiotic recombination hotspots in humans and mice. Science 327, 836–840.CrossRefGoogle Scholar
  3. Bishop, D.K., Park, D., Xu, L., and Kleckner, N. (1992). DMC1: a meiosis-specific yeast homolog of E. coli recA required for recombination, synaptonemal complex formation, and cell cycle progression. Cell 69, 439–456.CrossRefGoogle Scholar
  4. Borde, V., Robine, N., Lin, W., Bonfils, S., Géli, V., and Nicolas, A. (2009). Histone H3 lysine 4 trimethylation marks meiotic recombination initiation sites. EMBO J 28, 99–111.CrossRefGoogle Scholar
  5. Bulut-Karslioglu, A., De La Rosa-Velázquez, I.A., Ramirez, F., Barenboim, M., Onishi-Seebacher, M., Arand, J., Galán, C., Winter, G.E., Engist, B., Gerle, B., et al. (2014). Suv39h-dependent H3K9me3 marks intact retrotransposons and silences LINE elements in mouse embryonic stem cells. Mol Cell 55, 277–290.CrossRefGoogle Scholar
  6. Chen, S., Wang, J., Liu, S.J., Qin, Q.B., Xiao, J., Duan, W., Luo, K.K., Liu, J.H., and Liu, Y. (2009). Biological characteristics of an improved triploid crucian carp. Sci China Ser C-Life Sci 52, 733–738.CrossRefGoogle Scholar
  7. Costa, Y., Speed, R., Ollinger, R., Alsheimer, M., Semple, C.A., Gautier, P., Maratou, K., Novak, I., Höög, C., Benavente, R., et al. (2005). Two novel proteins recruited by synaptonemal complex protein 1 (SYCP1) are at the centre of meiosis. J Cell Sci 118, 2755–2762.CrossRefGoogle Scholar
  8. Eijpe, M., Offenberg, H., Jeßsberger, R., Revenkova, E., and Heyting, C. (2003). Meiotic cohesin REC8 marks the axial elements of rat synaptonemal complexes before cohesins SMC1⎲ and SMC3. J Cell Biol 160, 657–670.CrossRefGoogle Scholar
  9. Greer, E.L., and Shi, Y. (2012). Histone methylation: a dynamic mark in health, disease and inheritance. Nat Rev Genet 13, 343–357.CrossRefGoogle Scholar
  10. Gu, L., Wang, Q., and Sun, Q.Y. (2010). Histone modifications during mammalian oocyte maturation: dynamics, regulation and functions. Cell Cycle 9, 1942–1950.CrossRefGoogle Scholar
  11. Gu, L., Wang, Q., Wang, C.M., Hong, Y., Sun, S.G., Yang, S.Y., Wang, J. G., Hou, Y., Sun, Q.Y., and Liu, W.Q. (2008). Distribution and expression of phosphorylated histone H3 during porcine oocyte maturation. Mol Reprod Dev 75, 143–149.CrossRefGoogle Scholar
  12. Hamer, G., Gell, K., Kouznetsova, A., Novak, I., Benavente, R., and Höög, C. (2006). Characterization of a novel meiosis-specific protein within the central element of the synaptonemal complex. J Cell Sci 119, 4025–4032.CrossRefGoogle Scholar
  13. Handel, M.A., and Schimenti, J.C. (2010). Genetics of mammalian meiosis: regulation, dynamics and impact on fertility. Nat Rev Genet 11, 124–136.CrossRefGoogle Scholar
  14. Hayashi, K., Yoshida, K., and Matsui, Y. (2005). A histone H3 methyltransferase controls epigenetic events required for meiotic prophase. Nature 438, 374–378.CrossRefGoogle Scholar
  15. Hu, F., Xu, K., Zhou, Y., Wu, C., Wang, S., Xiao, J., Wen, M., Zhao, R., Luo, K., Tao, M., et al. (2017). Different expression patterns of sperm motility-related genes in testis of diploid and tetraploid cyprinid fish. Biol Reproduction 96, 907–920.CrossRefGoogle Scholar
  16. Hyun, K., Jeon, J., Park, K., and Kim, J. (2017). Writing, erasing and reading histone lysine methylations. Exp Mol Med 49, e324.CrossRefGoogle Scholar
  17. Ivanovska, I., and Orr-Weaver, T.L. (2006). Histone modifications and the chromatin scaffold for meiotic chromosome architecture. Cell Cycle 5, 2064–2071.CrossRefGoogle Scholar
  18. Kagawa, H. (2013). Oogenesis in Teleost Fish. (Aqua-bioscience monographs ABSM) pp. 99–127.Google Scholar
  19. Karimi, M.M., Goyal, P., Maksakova, I.A., Bilenky, M., Leung, D., Tang, J. X., Shinkai, Y., Mager, D.L., Jones, S., Hirst, M., et al. (2011). DNA methylation and SETDB1/H3K9me3 regulate predominantly distinct sets of genes, retroelements, and chimeric transcripts in mESCs. Cell Stem Cell 8, 676–687.CrossRefGoogle Scholar
  20. LaVoie, H.A. (2005). Epigenetic control of ovarian function: the emerging role of histone modifications. Mol Cellular Endocrinology 243, 12–18.CrossRefGoogle Scholar
  21. Lee, J.H., and Skalnik, D.G. (2008). Wdr82 is a C-terminal domain-binding protein that recruits the Setd1A Histone H3-Lys4 methyltransferase complex to transcription start sites of transcribed human genes. Mol Cellular Biol 28, 609–618.CrossRefGoogle Scholar
  22. Li, X.C., Barringer, B.C., and Barbash, D.A. (2009). The pachytene checkpoint and its relationship to evolutionary patterns of polyploidization and hybrid sterility. Heredity 102, 24–30.CrossRefGoogle Scholar
  23. Liu, S.J. (2010). Distant hybridization leads to different ploidy fishes. Sci China Life Sci 53, 416–425.CrossRefGoogle Scholar
  24. Liu, S., Liu, Y., Zhou, G., Zhang, X., Luo, C., Feng, H., He, X., Zhu, G., and Yang, H. (2001). The formation of tetraploid stocks of red crucian carp×common carp hybrids as an effect of interspecific hybridization. Aquaculture 192, 171–186.CrossRefGoogle Scholar
  25. Liu, S.J., Duan, W., Tao, M., Zhang, C., Sun, Y.D., Shen, J.M., Wang, J., Luo, K.K., and Liu, Y. (2007). Establishment of the diploid gynogenetic hybrid clonal line of red crucian carp×common carp. SCI CHINA SER C 50, 186–193.CrossRefGoogle Scholar
  26. Lubzens, E., Young, G., Bobe, J., and Cerdà, J. (2010). Oogenesis in teleosts: How fish eggs are formed. General Comp Endocrinology 165, 367–389.CrossRefGoogle Scholar
  27. Mallet, J. (2007). Hybrid speciation. Nature 446, 279–283.CrossRefGoogle Scholar
  28. Naumova, A.K., Fayer, S., Leung, J., Boateng, K.A., Camerini-Otero, R.D., and Taketo, T. (2013). Dynamics of response to asynapsis and meiotic silencing in spermatocytes from Robertsonian translocation carriers. PLoS ONE 8, e75970.CrossRefGoogle Scholar
  29. Neyton, S., Lespinasse, F., Moens, P.B., Paul, R., Gaudray, P., Paquis- Flucklinger, V., and Santucci-Darmanin, S. (2004). Association between MSH4 (MutS homologue 4) and the DNA strand-exchange RAD51 and DMC1 proteins during mammalian meiosis. MHR-Basic Sci reproductive Med 10, 917–924.CrossRefGoogle Scholar
  30. Ontoso, D., Kauppi, L., Keeney, S., and San Segundo, P.A. (2014). Dynamics of DOT1L localization and H3K79 methylation during meiotic prophase I in mouse spermatocytes. Chromosoma 123, 147–164.CrossRefGoogle Scholar
  31. Page, S.L., and Hawley, R.S. (2004). The genetics and molecular biology of the synaptonemal complex. Annu Rev Cell Dev Biol 20, 525–558.CrossRefGoogle Scholar
  32. Roeder, G., and Bailis, J.M. (2000). The pachytene checkpoint. Trends Genets 16, 395–403.CrossRefGoogle Scholar
  33. Strahl, B.D., and Allis, C.D. (2000). The language of covalent histone modifications. Nature 403, 41–45.CrossRefGoogle Scholar
  34. Tan, M., Luo, H., Lee, S., Jin, F., Yang, J.S., Montellier, E., Buchou, T., Cheng, Z., Rousseaux, S., Rajagopal, N., et al. (2011). Identification of 67 histone marks and histone lysine crotonylation as a new type of histone modification. Cell 146, 1016–1028.CrossRefGoogle Scholar
  35. Tao, M., Liu, S.J., Long, Y., Zeng, C., Liu, J.F., Liu, L.G., Zhang, C., Duan, W., and Liu, Y. (2008). The cloning of Dmc1 cDNAs and a comparative study of its expression in different ploidy cyprinid fishes. Sci China Ser C-Life Sci 51, 38–46.CrossRefGoogle Scholar
  36. Wang, J., Liu, Q., Luo, K., Chen, X., Xiao, J., Zhang, C., Tao, M., Zhao, R., and Liu, S. (2016). Cell fusion as the formation mechanism of unreduced gametes in the gynogenetic diploid hybrid fish. Sci Rep 6, 31658.CrossRefGoogle Scholar
  37. Wang, Q., Wang, C.M., Ai, J.S., Xiong, B., Yin, S., Hou, Y., Chen, D.Y., Schatten, H., and Sun, Q.Y. (2006a). Histone phosphorylation and pericentromeric histone modifications in oocyte meiosis. Cell Cycle 5, 1974–1982.CrossRefGoogle Scholar
  38. Wang, Q., Yin, S., Ai, J.S., Liang, C.G., Hou, Y., Chen, D.Y., Schatten, H., and Sun, Q.Y. (2006b). Histone deacetylation is required for orderly meiosis. Cell Cycle 5, 766–774.CrossRefGoogle Scholar
  39. Xu, D., Bai, J., Duan, Q., Costa, M., and Dai, W. (2009). Covalent modifications of histones during mitosis and meiosis. Cell Cycle 8, 3688–3694.CrossRefGoogle Scholar
  40. Xu, K., Wen, M., Duan, W., Ren, L., Hu, F., Xiao, J., Wang, J., Tao, M., Zhang, C., Wang, J., et al. (2015). Comparative analysis of testis transcriptomes from triploid and fertile diploid cyprinid fish. Biol Reproduction 92, 95.CrossRefGoogle Scholar
  41. Zhang, C., Liu, S.J., Wu, Y.H., and Liu, Y. (2015). DNA contents and cytological analysis on oogenesis of the diploid gynogenetic progeny of allotetraploid hybrids. J Fisheries China 39, 1–6.Google Scholar
  42. Zhou, R., Yang, F., Chen, D.F., Sun, Y.X., Yang, J.S., and Yang, W.J. (2013). Acetylation of chromatin-associated histone H3 lysine 56 inhibits the development of encysted artemia embryos. PLoS ONE 8, e68374.CrossRefGoogle Scholar
  43. Zhou, R., Xiao, J., Qin, Q., Zhu, B., Zhao, R., Zhang, C., Tao, M., Luo, K., Wang, J., Peng, L., et al. (2015). YY super sperm lead to all male triploids and tetraploids. BMC Genet 16, 68.CrossRefGoogle Scholar
  44. Zhou, Y., Zhong, H., Liu, S., Yu, F., Hu, J., Zhang, C., Tao, M., and Liu, Y. (2014). Elevated expression of Piwi and piRNAs in ovaries of triploid crucian carp. Mol Cellular Endocrinology 383, 1–9.CrossRefGoogle Scholar

Copyright information

© Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Rong Zhou
    • 1
  • Rujie Shang
    • 1
  • Dingbin Gong
    • 1
  • Xiujuan Xu
    • 1
  • Shaojun Liu
    • 1
    Email author
  1. 1.State Key Laboratory of Developmental Biology of Freshwater Fish, College of Life ScienceHunan Normal UniversityChangshaChina

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