胡桃坂計画研究代表、堀越計画研究分担による成果がNature Communications 誌に掲載されました!

Cryo-EM structures of the BAF-Lamin A/Ccomplex bound to nucleosomes

Naoki Horikoshi, Ryosuke Miyake, Chizuru Sogawa-Fujiwara,Mitsuo Ogasawara, Yoshimasa Takizawa, Hitoshi Kurumizaka

Barrier-to-autointegration factor (BAF) associates with mitotic chromosomesand promotes nuclear envelope assembly by recruiting proteins, such asLamins, 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 andaffect the chromatin organization remains elusive. Here we report the cryo-electron microscopy structures of BAF-Lamin A/C-nucleosome complexes. Wefind that the BAF dimer complexed with the Lamin A/C IgF domain occupiesthe nucleosomal dyad position, forminga tripartite nucleosomal DNA bindingstructure. We also show that the LaminA/C Lys486 and His506 residues, whichare reportedly mutated in lipodystrophy patients, directly contact the DNA atthe nucleosomal dyad. Excess BAF-Lamin A/C complexes symmetrically bindother nucleosomal DNA sites and connect two BAF-Lamin A/C-nucleosomecomplexes. Although the linker histone H1 competes with BAF-Lamin A/Cbinding at the nucleosomal dyad region, the two BAF-Lamin A/C molecules stillbridge two nucleosomes. Thesefindings provide insights into the mechanismby which BAF, Lamin A/C, and/or histone H1 bind nucleosomes and influence chromatin organization within the nucleus.

Nature Communications, doi: 10.1038/s41467-025-56823-9. (2025)
https://www.nature.com/articles/s41467-025-56823-9