東京大学 · Biochemistry, Genetics and Molecular Biology
히토시 히쿠루마자카 교수의 연구실은 염색체 구조와 기능의 핵심인 히스톤 변형체와 뉴클레오솜의 구조적 다양성, 특히 이들의 안정성과 역할에 초점을 맞추고 있습니다. 특히 정자 생성 과정에서의 히스톤 H3 변형체 H3T, DNA 복구에 관여하는 Xrcc3-Rad51C 복합체, 그리고 암과 관련된 히스톤 돌연변이(H2B E76K)의 기전을 구조생물학적 접근으로 규명하고 있습니다. 연구는 뉴클레오솜의 동적 특성과 염색질 재편성 메커니즘을 통해 유전자 발현 조절 및 세포 운명 결정의 분자 기전을 밝히는 데 기여하고 있습니다.
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A histone H3 variant, H3T, is highly expressed in the testis, suggesting that it may play an important role in the chromatin reorganization required for meiosis and/or spermatogenesis. In the present study, we found that the nucleosome containing human H3T is significantly unstable both in vitro and in vivo, as compared to the conventional nucleosome containing H3.1. The crystal structure of the H3T nucleosome revealed structural differences in the H3T regions on both ends of the central alpha2
The human Xrcc3 protein is involved in the repair of damaged DNA through homologous recombination, in which homologous pairing is a key step. The Rad51 protein is believed to be the only protein factor that promotes homologous pairing in recombinational DNA repair in mitotic cells. In the brain, however, Rad51 expression is extremely low, whereas XRCC3, a human homologue of Saccharomyces cerevisiae RAD57 that activates the Rad51-dependent homologous pairing with the yeast Rad55 protein, is expre
In eukaryotes, genomic DNA is compacted in chromatin, which generally suppresses transcription, replication, repair, and recombination. The fundamental unit of chromatin is the nucleosome, whose structure was first determined at atomic resolution in 1997. However, recent findings have revealed that the nucleosome is not a structurally homogenous entity. Nucleosomes containing histone variants often have subtle but clear differences in their structural and functional characteristics, as compared
Nucleosomes are dynamic entities that are repositioned along DNA by chromatin remodeling processes. A nucleosome repositioned by the switch-sucrose nonfermentable (SWI/SNF) remodeler collides with a neighbor and forms the intermediate "overlapping dinucleosome." Here, we report the crystal structure of the overlapping dinucleosome, in which two nucleosomes are associated, at 3.14-angstrom resolution. In the overlapping dinucleosome structure, the unusual "hexasome" nucleosome, composed of the hi
Mutations of the Glu76 residue of canonical histone H2B are frequently found in cancer cells. However, it is quite mysterious how a single amino acid substitution in one of the multiple H2B genes affects cell fate. Here we found that the H2B E76K mutation, in which Glu76 is replaced by Lys (E76K), distorted the interface between H2B and H4 in the nucleosome, as revealed by the crystal structure and induced nucleosome instability in vivo and in vitro. Exogenous production of the H2B E76K mutant r
Chromatin compacts genomic DNA in eukaryotes. The primary chromatin unit is the nucleosome core particle, composed of four pairs of the core histones, H2A, H2B, H3, and H4, and 145-147 base pairs of DNA. Since replication, recombination, repair, and transcription take place in chromatin, the structure and dynamics of the nucleosome must be versatile. These nucleosome characteristics underlie the epigenetic regulation of genomic DNA. In higher eukaryotes, many histone variants have been identifie
