TY - JOUR
T1 - Crystal Structure and Characterization of Novel Human Histone H3 Variants, H3.6, H3.7, and H3.8
AU - Taguchi, Hiroyuki
AU - Xie, Yan
AU - Horikoshi, Naoki
AU - Maehara, Kazumitsu
AU - Harada, Akihito
AU - Nogami, Jumpei
AU - Sato, Koichi
AU - Arimura, Yasuhiro
AU - Osakabe, Akihisa
AU - Kujirai, Tomoya
AU - Iwasaki, Takeshi
AU - Semba, Yuichiro
AU - Tachibana, Taro
AU - Kimura, Hiroshi
AU - Ohkawa, Yasuyuki
AU - Kurumizaka, Hitoshi
PY - 2017/4/25
Y1 - 2017/4/25
N2 - 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.
AB - 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.
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U2 - 10.1021/acs.biochem.6b01098
DO - 10.1021/acs.biochem.6b01098
M3 - Article
C2 - 28374988
AN - SCOPUS:85018642720
SN - 0006-2960
VL - 56
SP - 2184
EP - 2196
JO - Biochemistry
JF - Biochemistry
IS - 16
ER -