The study reveals cryo-electron microscopy structures of the BAF-Lamin A/C complex when bound to nucleosomes, providing insights on chromatin organization.
The research outlines the cryo-electron microscopy structures of BAF-Lamin A/C-nucleosome complexes, elucidates the mechanism of how BAF and Lamin A/C bind to nucleosomes and influence chromatin organization.
The study was conducted by researchers affiliated with various institutions, including the Japan Society for the Promotion of Science.
The article was published on September 4, 2025.
The research took place at the University of Tokyo and involved collaboration with other academic institutions.
The study aims to clarify how BAF and Lamin A/C interact with chromatin, which is significant for nuclear envelope assembly and chromatin organization, particularly due to its links to laminopathies influenced by mutations.
The research employed cryo-electron microscopy to visualize the structures of BAF-Lamin A/C-nucleosome complexes, along with biochemical assays to analyze nucleosome binding and effects of specific mutations.
Mutations at residues Lys486 and His506 on Lamin A/C disrupt nucleosome binding, associated with lipodystrophy patients and chromatin disorganization.
“These findings provide insights on the mechanism by which BAF, Lamin A/C, and/or histone H1 bind nucleosomes and influence chromatin organization within the nucleus.”
“We found a previously unrecognized DNA-binding interface of Lamin A/C, including the Lys486 and His506 residues.”
“The impairments of chromatin anchoring to the nuclear lamina, particularly observed through mutated Lamin A/C, may lead to chromatin disorganization seen in patients.”
“Our determination of cryo-EM structures exemplifies the complex interplay between BAF and Lamin A/C during chromatin organization.”
The article will open by highlighting the importance of BAF and Lamin A/C complexes and their role in chromatin organization, capturing reader interest with the significance of the new cryo-EM findings. Quotes may introduce BAF's and Lamin A/C's relevance.
This section will cover what chromatin is, its importance for gene regulation, and how BAF and Lamin A/C are involved with the nuclear lamina, setting the groundwork for the new discoveries and why they matter.
Here, details on cryo-EM methods and the step-by-step process of how chromatin complexes were analyzed will be laid out, supported by specific findings and selected quotes.
The core results will be presented, emphasizing how the structures elucidate chromatin organization mechanisms and their potential impacts on diseases related to lamina protein mutations, integrating relevant quotes to underpin findings.
The article will summarize the key discoveries, addressing future research directions related to BAF-Lamin complexes and their potential therapeutic relevance, leaving the reader with impactful takeaways from the study.