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

Takashi Urahama, Akihito Harada, Kazumitsu Maehara, Naoki Horikoshi, Koichi Sato, Yuko Sato, Koji Shiraishi, Norihiro Sugino, Akihisa Osakabe, Hiroaki Tachiwana, Wataru Kagawa, Hiroshi Kimura, Yasuyuki Ohkawa, Hitoshi Kurumizaka

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number51
JournalEpigenetics and Chromatin
Volume9
Issue number1
DOIs
Publication statusPublished - 2016 Jan 15

Keywords

  • Chromatin
  • Histone variant
  • Nucleosome
  • Spermatogenesis
  • Testis
  • Transcription start site

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology

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