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First-Ever Clarification of Structural Basis of Human Testis Chromosomes (Press Release)

Release Date
25 May, 2010
  • BL41XU (Structural Biology I)
Clarification of instability of basic structure and structural basis of human testis chromosomes, which are important for spermatogenesis

Waseda University

Hitoshi Kurumizaka, Professor in the Faculty of Science and Engineering, Waseda University, and his colleagues succeeded in clarifying the instability of the basic structure and the structural basis of human testis chromosomes, which are important for spermatogenesis.  The achievements will lead to the clarification of the disruption of spermatogenesis, which is considered to be the major cause of male sterility and will contribute to the progress of reproductive medicine.  The achievements were published as a research paper in the online version of the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS).

Publication:
"Structural basis of instability of the nucleosome containing a testis-specific histone variant, human H3T"
Hiroaki Tachiwana, Wataru Kagawa, Akihisa Osakabe, Koichiro Kawaguchi, Tatsuya Shiga, Yoko Hayashi-Takanaka, Hiroshi Kimura, and Hitoshi Kurumizaka
Proceedings of the National Academy of Sciences 107(23), 10454-10459 (2010), ｐublished online May 24, 2010

The genetic information of all living organisms is transmitted to offspring via genomic DNA.  In organisms having sexual reproduction such as humans, the maternal genomic DNA is stored in the egg and the paternal genomic DNA is stored in sperm.  When the egg and sperm unite by fertilization, the outcome is a biological individual having the genomic DNA of both parents.  The genomic DNA is stored as chromosomes in the nucleus.  The basic structure of chromosomes is the nucleosome, which has a disklike shape in which the double-stranded DNA winds around a histone octamer consisting of two molecules each of the four types of the protein called histone (H2A, H2B, H3, and H4).

However, it has recently been reported that this nucleosome structure is maintained in only 4% of the nuclei of sperms compared with that of ordinary cells (Fig. 1).  Since H3T, a variant of histone H3, is highly expressed in the testis where sperms are produced, it has been considered that histone H3T is important for the structural formation of the sperm chromosomes.  However, the function and structure of histone H3T have remained unknown.  Researchers have also reported that the nucleosome of sperm nuclei functions as an epigenetic marker of the genes that are expressed after fertilization.  The significance of histone H3T is now attracting attention. 

In this study, we succeeded in reconstructing the nucleosome con　taining human-derived histone H3T and clarifying its three-dimensional structure by X-ray crystal structural analysis with atomic-level resolution for the first time in the world using the Structural Biology I Beamline BL41XU at SPring-8 (Fig. 2).  The nucleosome containing histone H3T was found to be significantly unstable compared with the nucleosome containing the regular histone H3.  By three-dimensional structural and biochemical analyses, we also found that the major cause of this instability of the nucleosome containing histone H3T is the 111th valine residue, which is specific to histone H3T.  

From these results, we clarified the three-dimensional structure and structural properties of histone H3T, which have been unknown, and also provided some basic findings for understanding the formation of sperms and eggs through meiosis and the formation mechanisms of sperm nuclei.  Moreover, the three-dimensional structure of the nucleosome observed in this study is the basic structure for clarifying the mechanism of the transmission of the information on the epigenetic expression of genomic DNA of a fertilized egg, which is mediated by the nucleosome structure of sperm nuclei. 

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Fig. 1

Fig. 1

Fig. 2

Fig. 2


For more information, please contact:
Prof. Hitoshi KURUMIZAKA (Waseda University)
E-mail: mail

Dr. Hiroaki TACHIWANA (Waseda University)
E-mail: mail