研究実績
2026
3.
Naoki Horikoshi, Hitoshi Kurumizaka
Nucleosome Bundling by Barrier‐to‐Autointegration Factor: Implications for Its Diverse Functions Journal Article
In: BioEssays, vol. 48, no. 1, 2026, ISSN: 1521-1878.
Abstract | Links | タグ: Horikoshi G, Kurumizaka G
@article{Horikoshi2026,
title = {Nucleosome Bundling by Barrier‐to‐Autointegration Factor: Implications for Its Diverse Functions},
author = {Naoki Horikoshi and Hitoshi Kurumizaka},
doi = {10.1002/bies.70104},
issn = {1521-1878},
year = {2026},
date = {2026-01-22},
journal = {BioEssays},
volume = {48},
number = {1},
publisher = {Wiley},
abstract = {In eukaryotic cells, genomic DNA is packaged into chromatin, restricting the access of regulatory proteins and thus regulating key processes such as transcription, replication, recombination, and the repair of DNA. Barrier-to-autointegration factor (BAF) plays key roles in organizing chromatin architecture and nuclear functions. BAF bridges DNA segments and connects them to Lamin A/C and inner nuclear membrane proteins containing the LEM domain, ensuring proper chromatin organization and nuclear envelope assembly and repair. Over the last three decades, multiple structural studies have revealed that BAF dimerizes to bind DNA and shapes higher-order chromatin structure. In this review, we summarize the structural features of BAF in complexes with its binding partners and explore how these interactions contribute to maintaining nuclear integrity and regulating genome function.},
keywords = {Horikoshi G, Kurumizaka G},
pubstate = {published},
tppubtype = {article}
}
In eukaryotic cells, genomic DNA is packaged into chromatin, restricting the access of regulatory proteins and thus regulating key processes such as transcription, replication, recombination, and the repair of DNA. Barrier-to-autointegration factor (BAF) plays key roles in organizing chromatin architecture and nuclear functions. BAF bridges DNA segments and connects them to Lamin A/C and inner nuclear membrane proteins containing the LEM domain, ensuring proper chromatin organization and nuclear envelope assembly and repair. Over the last three decades, multiple structural studies have revealed that BAF dimerizes to bind DNA and shapes higher-order chromatin structure. In this review, we summarize the structural features of BAF in complexes with its binding partners and explore how these interactions contribute to maintaining nuclear integrity and regulating genome function.
2025
2.
Suguru Hatazawa, Naoki Horikoshi, Hitoshi Kurumizaka
Structural diversity of noncanonical nucleosomes: Functions in chromatin Journal Article
In: Current Opinion in Structural Biology, vol. 92, pp. 103054, 2025, ISSN: 0959-440X.
Abstract | Links | タグ: Horikoshi G, Kurumizaka G
@article{HATAZAWA2025103054,
title = {Structural diversity of noncanonical nucleosomes: Functions in chromatin},
author = {Suguru Hatazawa and Naoki Horikoshi and Hitoshi Kurumizaka},
url = {https://www.sciencedirect.com/science/article/pii/S0959440X25000727},
doi = {https://doi.org/10.1016/j.sbi.2025.103054},
issn = {0959-440X},
year = {2025},
date = {2025-04-30},
urldate = {2025-01-01},
journal = {Current Opinion in Structural Biology},
volume = {92},
pages = {103054},
abstract = {In eukaryotes, genomic DNA is compacted into chromatin, with nucleosomes acting as its basic structural units. In addition to canonical nucleosomes, noncanonical nucleosomes, such as hexasomes, H3–H4 octasomes, and overlapping dinucleosomes, exhibit alternative histone compositions and play key roles in chromatin remodeling, transcription, and replication. Recent cryo-electron microscopy (cryo-EM) studies have elucidated the structural details of these noncanonical nucleosomes and their interactions with histone chaperones and chromatin remodelers. This review highlights recent advances in the structural and functional understanding of noncanonical nucleosomes and their roles in maintaining chromatin integrity and facilitating transcriptional dynamics.},
keywords = {Horikoshi G, Kurumizaka G},
pubstate = {published},
tppubtype = {article}
}
In eukaryotes, genomic DNA is compacted into chromatin, with nucleosomes acting as its basic structural units. In addition to canonical nucleosomes, noncanonical nucleosomes, such as hexasomes, H3–H4 octasomes, and overlapping dinucleosomes, exhibit alternative histone compositions and play key roles in chromatin remodeling, transcription, and replication. Recent cryo-electron microscopy (cryo-EM) studies have elucidated the structural details of these noncanonical nucleosomes and their interactions with histone chaperones and chromatin remodelers. This review highlights recent advances in the structural and functional understanding of noncanonical nucleosomes and their roles in maintaining chromatin integrity and facilitating transcriptional dynamics.
1.
Naoki Horikoshi, Ryosuke Miyake, Chizuru Sogawa-Fujiwara, Mitsuo Ogasawara, Yoshimasa Takizawa, Hitoshi Kurumizaka
Cryo-EM structures of the BAF-Lamin A/C complex bound to nucleosomes Journal Article
In: Nat Commun, vol. 16, no. 1, 2025, ISSN: 2041-1723.
Abstract | Links | タグ: Horikoshi G, Kurumizaka G
@article{Horikoshi2025,
title = {Cryo-EM structures of the BAF-Lamin A/C complex bound to nucleosomes},
author = {Naoki Horikoshi and Ryosuke Miyake and Chizuru Sogawa-Fujiwara and Mitsuo Ogasawara and Yoshimasa Takizawa and Hitoshi Kurumizaka},
doi = {10.1038/s41467-025-56823-9},
issn = {2041-1723},
year = {2025},
date = {2025-02-10},
journal = {Nat Commun},
volume = {16},
number = {1},
publisher = {Springer Science and Business Media LLC},
abstract = {<jats:title>Abstract</jats:title>
<jats:p>Barrier-to-autointegration factor (BAF) associates with mitotic chromosomes and promotes nuclear envelope assembly by recruiting proteins, such as Lamins, required for the reconstruction of the nuclear envelope and lamina. BAF also mediates chromatin anchoring to the nuclear lamina via Lamin A/C. However, the mechanism by which BAF and Lamin A/C bind chromatin and affect the chromatin organization remains elusive. Here we report the cryo-electron microscopy structures of BAF-Lamin A/C-nucleosome complexes. We find that the BAF dimer complexed with the Lamin A/C IgF domain occupies the nucleosomal dyad position, forming a tripartite nucleosomal DNA binding structure. We also show that the Lamin A/C Lys486 and His506 residues, which are reportedly mutated in lipodystrophy patients, directly contact the DNA at the nucleosomal dyad. Excess BAF-Lamin A/C complexes symmetrically bind other nucleosomal DNA sites and connect two BAF-Lamin A/C-nucleosome complexes. Although the linker histone H1 competes with BAF-Lamin A/C binding at the nucleosomal dyad region, the two BAF-Lamin A/C molecules still bridge two nucleosomes. These findings provide insights into the mechanism by which BAF, Lamin A/C, and/or histone H1 bind nucleosomes and influence chromatin organization within the nucleus.</jats:p>},
keywords = {Horikoshi G, Kurumizaka G},
pubstate = {published},
tppubtype = {article}
}
<jats:title>Abstract</jats:title>
<jats:p>Barrier-to-autointegration factor (BAF) associates with mitotic chromosomes and promotes nuclear envelope assembly by recruiting proteins, such as Lamins, required for the reconstruction of the nuclear envelope and lamina. BAF also mediates chromatin anchoring to the nuclear lamina via Lamin A/C. However, the mechanism by which BAF and Lamin A/C bind chromatin and affect the chromatin organization remains elusive. Here we report the cryo-electron microscopy structures of BAF-Lamin A/C-nucleosome complexes. We find that the BAF dimer complexed with the Lamin A/C IgF domain occupies the nucleosomal dyad position, forming a tripartite nucleosomal DNA binding structure. We also show that the Lamin A/C Lys486 and His506 residues, which are reportedly mutated in lipodystrophy patients, directly contact the DNA at the nucleosomal dyad. Excess BAF-Lamin A/C complexes symmetrically bind other nucleosomal DNA sites and connect two BAF-Lamin A/C-nucleosome complexes. Although the linker histone H1 competes with BAF-Lamin A/C binding at the nucleosomal dyad region, the two BAF-Lamin A/C molecules still bridge two nucleosomes. These findings provide insights into the mechanism by which BAF, Lamin A/C, and/or histone H1 bind nucleosomes and influence chromatin organization within the nucleus.</jats:p>
<jats:p>Barrier-to-autointegration factor (BAF) associates with mitotic chromosomes and promotes nuclear envelope assembly by recruiting proteins, such as Lamins, required for the reconstruction of the nuclear envelope and lamina. BAF also mediates chromatin anchoring to the nuclear lamina via Lamin A/C. However, the mechanism by which BAF and Lamin A/C bind chromatin and affect the chromatin organization remains elusive. Here we report the cryo-electron microscopy structures of BAF-Lamin A/C-nucleosome complexes. We find that the BAF dimer complexed with the Lamin A/C IgF domain occupies the nucleosomal dyad position, forming a tripartite nucleosomal DNA binding structure. We also show that the Lamin A/C Lys486 and His506 residues, which are reportedly mutated in lipodystrophy patients, directly contact the DNA at the nucleosomal dyad. Excess BAF-Lamin A/C complexes symmetrically bind other nucleosomal DNA sites and connect two BAF-Lamin A/C-nucleosome complexes. Although the linker histone H1 competes with BAF-Lamin A/C binding at the nucleosomal dyad region, the two BAF-Lamin A/C molecules still bridge two nucleosomes. These findings provide insights into the mechanism by which BAF, Lamin A/C, and/or histone H1 bind nucleosomes and influence chromatin organization within the nucleus.</jats:p>
