Crystal Structure and Characterization of Novel Human Histone H3 Variants, H3.6, H3.7, and H3.8

Hiroyuki Taguchi, Yan Xie, Naoki Horikoshi, Kazumitsu Maehara, Akihito Harada, Jumpei Nogami, Koichi Sato, Yasuhiro Arimura, Akihisa Osakabe, Tomoya Kujirai, Takeshi Iwasaki, Yuichiro Semba, Taro Tachibana, Hiroshi Kimura, Yasuyuki Ohkawa, Hitoshi Kurumizaka

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Non-allelic histone variants are considered as epigenetic factors that regulate genomic DNA functions in eukaryotic chromosomes. In this study, we identified three new human histone H3 variants (named H3.6, H3.7, and H3.8), which were previously annotated as pseudogenes. H3.6 and H3.8 conserve the H3.3-specific amino acid residues, but H3.7 shares the specific amino acid residues with H3.1. We successfully reconstituted the nucleosome containing H3.6 in vitro and determined its crystal structure. In the H3.6 nucleosome, the H3.6-specific Val62 residue hydrophobically contacts the cognate H4 molecule, but its contact area is smaller than that of the corresponding H3.3 Ile62 residue. The thermal stability assay revealed that the H3.6 nucleosome is substantially unstable, as compared to the H3.3 nucleosome. Interestingly, mutational analysis demonstrated that the H3.6 Val62 residue is fully responsible for the H3.6 nucleosome instability, probably because of the weakened hydrophobic interaction with H4. We also reconstituted the nucleosome containing H3.8, but its thermal stability was quite low. In contrast, purified H3.7 failed to form nucleosomes in vitro. The identification and characterization of these novel human histone H3 variants provide important new insights into understanding the epigenetic regulation of the human genome.

元の言語英語
ページ(範囲)2184-2196
ページ数13
ジャーナルBiochemistry
56
発行部数16
DOI
出版物ステータス出版済み - 4 25 2017

All Science Journal Classification (ASJC) codes

  • Biochemistry

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    Taguchi, H., Xie, Y., Horikoshi, N., Maehara, K., Harada, A., Nogami, J., Sato, K., Arimura, Y., Osakabe, A., Kujirai, T., Iwasaki, T., Semba, Y., Tachibana, T., Kimura, H., Ohkawa, Y., & Kurumizaka, H. (2017). Crystal Structure and Characterization of Novel Human Histone H3 Variants, H3.6, H3.7, and H3.8. Biochemistry, 56(16), 2184-2196. https://doi.org/10.1021/acs.biochem.6b01098