Our research focuses on epigenetic dynamics during mammalian germ cell development and fertilization. Epigenetic inheritance from arents to progeny has been catching a huge attention, thus our research can contribute to elucidate the mechanism.

About Research

Epigenetics : Supporting proper transgenerational transmission of genetic information

Epigenetics supports proper transmission of genetic information to progeny. Germ cells undergo dynamic morphological and molecular changes in order to transfer their genetic information to the progeny. For example, in sperm nuclei, which major axis is only 5 micrometer due to the histone removal and intense chromatin condenstaion, most of the nuclear events such as transcription and translation are thought to be shut-off. However, recent studies indicate that small amount of histones as well as RNAs still exist in mature sperm, and suggest the possibility that these histones and RNAs play some roles during fertilization. More recently, it is demonstranted that transient stress occurs in male individuals causes epigenetic alteration, and the altered epigenetic marks are inheritable to progeny. These observations support the idea that sperm transfer something other than their genome to the progeny.
In our laboratory, we focus on the chromatin dynamics in germ cells, and examine how it contributes cell proliferation, diff erentiation and fertilization, and three specific projects are on-going; i) identification and analysis of chromatin modifiers important for spermatogonial stem cells (SSCs), ii) investigating the roles of histone variants during spermatogenesis, and iii) profiling of histones retained in sperm and functional analysis of sperm histone variants.

Summary of our research projects. We are investigating the epigenetic dynamics from spermatogenesis to fertilization by using mice.



  1. KM mutant highlights enhancers in minor ZGA.
    Okada Y, Aoshima K.
    Cell Cycle. 2015 Aug 18;14(16):2541-2. doi: 10.1080/15384101.2015.1060774
  2. Paternal H3K4 methylation is required for minor zygotic gene activation and early mouse embryonic development.
    Aoshima K, Inoue E, Sawa H, Okada Y.
    EMBO Rep. 2015 Jul;16(7):803-12. doi: 10.15252/embr.201439700.
  3. Generation of a dual-color reporter mouse line to monitor spermatogenesis in vivo.
    Makino Y, Inoue E, Hada M, Aoshima K, Kitano S, Miyachi H, Okada Y.
    Front Cell Dev Biol. 2014 Jul 23;2:30. doi: 10.3389/fcell.2014.00030.
  4. Establishment of alternative culture method for spermatogonial stem cells using knockout serum replacement.
    Aoshima K, Baba A, Makino Y, Okada Y.
    PLoS One. 2013 Oct 28;8(10):e77715. doi: 10.1371/journal.pone.0077715.
  5. Understanding paternal genome demethylation through live-cell imaging and siRNA.
    Yamagata K, Okada Y.
    Cell Mol Life Sci. 2011 May;68(10):1669-79. doi: 10.1007/s00018-010-0623-0
  6. A role for the elongator complex in zygotic paternal genome demethylation.
    Okada Y, Yamagata K, Hong K, Wakayama T, Zhang Y.
    Nature. 2010 Jan 28;463(7280):554-8. doi: 10.1038/nature08732.
  7. Histone demethylase JHDM2A is involved in male infertility and obesity.
    Okada Y, Tateishi K, Zhang Y.
    J Androl. 2010 Jan-Feb;31(1):75-8. doi: 10.2164/jandrol.109.008052.Review.
  8. Histone demethylase JHDM2A is critical for Tnp1 and Prm1 transcription and spermatogenesis.
    Okada Y, Scott G, Ray MK, Mishina Y, Zhang Y.
    Nature. 2007 Nov 1;450(7166):119-23.
  9. Leukaemic transformation by CALM-AF10 involves upregulation of Hoxa5 by hDOT1L.
    Okada Y, Jiang Q, Lemieux M, Jeannotte L, Su L, Zhang Y.
    Nat Cell Biol. 2006 Sep;8(9):1017-24.
  10. hDOT1L links histone methylation to leukemogenesis.
    Okada Y, Feng Q, Lin Y, Jiang Q, Li Y, Coffield VM, Su L, Xu G, Zhang Y.
    Cell. 2005 Apr 22;121(2):167-78.
Yuki Okada
Pharmaceutical Sciences, Graduate School of Arts and Sciences
Yasuhiro Fujiwara
Research Associate
Masashi Hada
Research Associate
Erina Inoue
Technical Specialist