Histone H3.5 forms an unstable nucleosome and accumulates around transcription start sites in human testis

Epigenetics & Chromatin

Hitoshi Kurumizaka²  Yasuyuki Ohkawa⁴  Hiroshi Kimura³  Wataru Kagawa⁵  Hiroaki Tachiwana²  Akihisa Osakabe²  Norihiro Sugino¹  Koji Shiraishi¹  Yuko Sato³  Koichi Sato²  Naoki Horikoshi²  Kazumitsu Maehara⁴  Akihito Harada⁴  Takashi Urahama² 

[1] Faculty of Medicine and Health Sciences, Yamaguchi University, 1-1-1 Minami-Kogushi, Ube 755-8505, Japan;Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Institute for Medical-oriented Structural Biology, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan;Department of Biological Sciences, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama 226-8501, Japan;Division of Transcriptomics, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Fukuoka, Japan;Program in Chemistry and Life Science, School of Science and Engineering, Meisei University, 2-1-1 Hodokubo, Hino 191-8506, Tokyo, Japan

关键词: Transcription start site;    Spermatogenesis;    Testis;    Chromatin;    Nucleosome;    Histone variant;   

Others  :  1235367
DOI  :  10.1186/s13072-016-0051-y

 received in 2015-10-17, accepted in 2016-01-05,  发布年份 2016

【 摘 要 】

Background

Human histone H3.5 is a non-allelic H3 variant evolutionally derived from H3.3. The H3.5 mRNA is highly expressed in human testis. However, the function of H3.5 has remained poorly understood.

Results

We found that the H3.5 nucleosome is less stable than the H3.3 nucleosome. The crystal structure of the H3.5 nucleosome showed that the H3.5-specific Leu103 residue, which corresponds to the H3.3 Phe104 residue, reduces the hydrophobic interaction with histone H4. Mutational analyses revealed that the H3.5-specific Leu103 residue is responsible for the instability of the H3.5 nucleosome, both in vitro and in living cells. The H3.5 protein was present in human seminiferous tubules, but little to none was found in mature sperm. A chromatin immunoprecipitation coupled with sequencing analysis revealed that H3.5 accumulated around transcription start sites (TSSs) in testicular cells.

Conclusions

We performed comprehensive studies of H3.5, and found the instability of the H3.5 nucleosome and the accumulation of H3.5 protein around TSSs in human testis. The unstable H3.5 nucleosome may function in the chromatin dynamics around the TSSs, during spermatogenesis.

【 授权许可】

   
2016 Urahama et al.

【 图 表 】

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