title: Crystal Structure and Characterization of Novel Human Histone H3 Variants, H3.6, H3.7, and H3.8.
abstract: 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.
authors.affiliation: Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Research Institute for Science and Engineering, and Institute for Medical-oriented Structural Biology, Waseda University , 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Taguchi
authors.affiliation: Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Research Institute for Science and Engineering, and Institute for Medical-oriented Structural Biology, Waseda University , 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Research Institute for Science and Engineering, and Institute for Medical-oriented Structural Biology, Waseda University , 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Horikoshi
authors.affiliation: Division of Transcriptomics, Medical Institute of Bioregulation, Kyushu University , 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Kazumitsu
authors.initials: K
authors.lastname: Maehara
authors.affiliation: Division of Transcriptomics, Medical Institute of Bioregulation, Kyushu University , 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Akihito
authors.initials: A
authors.lastname: Harada
authors.affiliation: Division of Transcriptomics, Medical Institute of Bioregulation, Kyushu University , 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Jumpei
authors.initials: J
authors.lastname: Nogami
authors.affiliation: Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Research Institute for Science and Engineering, and Institute for Medical-oriented Structural Biology, Waseda University , 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Sato
authors.affiliation: Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Research Institute for Science and Engineering, and Institute for Medical-oriented Structural Biology, Waseda University , 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Arimura
authors.affiliation: Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Research Institute for Science and Engineering, and Institute for Medical-oriented Structural Biology, Waseda University , 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
authors.forename: Akihisa
authors.initials: A
authors.lastname: Osakabe
authors.affiliation: Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Research Institute for Science and Engineering, and Institute for Medical-oriented Structural Biology, Waseda University , 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Kujirai
authors.affiliation: Division of Transcriptomics, Medical Institute of Bioregulation, Kyushu University , 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Iwasaki
authors.affiliation: Division of Transcriptomics, Medical Institute of Bioregulation, Kyushu University , 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Semba
authors.affiliation: Department of Bioengineering, Graduate School of Engineering, Osaka City University , Sugimoto, Sumiyoshi-ku, Osaka 558-8585, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Tachibana
authors.affiliation: Cell Biology Unit, Institute of Innovative Research, Tokyo Institute of Technology , 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kimura
authors.affiliation: Division of Transcriptomics, Medical Institute of Bioregulation, Kyushu University , 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Ohkawa
authors.affiliation: Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Research Institute for Science and Engineering, and Institute for Medical-oriented Structural Biology, Waseda University , 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
authors.forename: Hitoshi
authors.identifier: 0000-0001-7412-3722
authors.initials: H
authors.lastname: Kurumizaka
mesh_terms: D002843:Chromatin / Q000378:metabolism; D018360:Crystallography, X-Ray; D006657:Histones / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D011487:Protein Conformation; D020033:Protein Isoforms / Q000737:chemistry*
chemical_list: D002843:Chromatin; D006657:Histones; D020033:Protein Isoforms