Research
The Arimura Lab is focused on understanding the structure and function of chromatin. Throughout cellular differentiation and the many stages of the cell cycle, chromatin undergoes dynamic changes in its structure. There are various types of chromatin regions with specific functions, such as euchromatin (transcriptionally active regions), heterochromatin (transcriptionally inactive regions), telomeres (regions protecting chromosome ends), centromeres (regions forming kinetochores), transcription start sites, and compacted M-phase chromatin. Dysregulation of chromatin structures can lead to aberrant gene expression or aneuploidy, resulting in various diseases including cancer. The specific local chromatin structures in each type of chromatin region are therefore thought to play an instrumental role in exerting their specific functions. However, it remains unclear what local chromatin structures are formed in these regions and how these chromatin structures control the events on chromatin. My lab aims to elucidate these mechanisms by identifying the structural basis of diverse chromatin functions by developing novel cryo-EM based methods.
Selected publications:
- #corresponding author
- *co-first author
- MagIC-Cryo-EM: Structural determination on magnetic beads for scarce macromolecules in heterogeneous samples Arimura Y, Konishi Hide A., Funabiki H. bioRxiv (2024)
- Structural features of nucleosomes in interphase and metaphase chromosomes Arimura Y#, Shih MR, Froom R, Funabiki H#. Mol Cell 81, 4377-4397 (2021)
- The CENP-A centromere targeting domain facilitates H4K20 monomethylation in the nucleosome by structural polymorphism Arimura Y*, Tachiwana H*, Takagi H*, Hori T, Kimura H, Fukagawa T, Kurumizaka H. Nature Commun. 10, 576 (2019)
- Cancer-associated mutations of histones H2B, H3.1 and H2A.Z.1 affect the structure and stability of the nucleosome Arimura Y, Ikura M, Fujita R, Noda M,...., Kurumizaka H. Nucleic Acids Res. 46, 10007-10018 (2018)
Research:
Eukaryotic chromatin undergoes dynamic changes in its structure during cellular differentiation and in each stage of the cell cycle. Various types of chromatin regions with specific functions, such as euchromatin (transcriptionally active regions), heterochromatin (transcriptionally inactive regions), telomeres (regions protecting chromosome ends), centromeres (regions forming kinetochores), transcription start sites, and compacted M-phase chromatin, are established. Dysregulation of chromatin structures can lead to aberrant gene expression or aneuploidy, resulting in various diseases including cancer. The specific local chromatin structures in each type of chromatin region are therefore thought to play an instrumental role in exerting their specific functions. However, it remains unclear what local chromatin structures are formed in these regions and how these chromatin structures control the events on chromatin.
My lab aims to elucidate these mechanisms by identifying the structural basis of diverse chromatin functions by using the following approaches:
Structural analyses of chromatin-related complexes formed in the cellular environments
Despite extensive research on chromatin function, there remain many challenges in identifying the structural mechanisms of chromatin regulation. This challenge arises from the inability to determine nanometer-scale chromatin structures. To address this, we are developing innovative methods based on cryo-EM (cryo-electron microscopy) and cryo-ET (cryo-electron tomography) to directly analyze the structures of fundamental components and the three-dimensional folding of chromatin formed in cellular environments.
The method we previously developed has enabled the isolation and structural determination of nucleosomes formed in interphase and metaphase chromosomes. In addition, to enable the structural determination of specific chromatin-related complexes of interest, we have developed an innovative method, in which we can determine high-resolution structures of particular target complexes using crude cellular fractions containing only a few nanograms of the target complexes. This requirement is approximately 1000 times lower than the sample requirements of conventional cryo-EM, enabling the structural determination of endogenous chromatin-related complexes in cells. Our lab plans to further update these methods by combining cryo-ET and Next-Generation Sequencing (NGS) techniques to investigate the 3D chromatin structures formed in each chromatin region. We will apply these techniques to diverse cell types and chromatin regions, including euchromatin, heterochromatin, telomeres, and centromeres. These structures contain fundamental information necessary for understanding how chromatin structures regulate processes such as transcription, DNA replication, chromatin compaction, DNA repair, and chromosome segregation.
Assembling functional chromosomes in a test tube to investigate the mechanisms of chromatin formation
Along with revealing the structural components of chromatin, we also strive to understand how chromatin structures are established by reconstituting functional chromatin in a test tube. The Xenopus egg extract is a unique system that allows the reconstitution of functional interphase and M-phase chromosomes in a cell-free environment. By adding sperm to the Xenopus egg extract, chromatin-related proteins assemble on sperm cell DNA to form chromosomes. The Xenopus egg extract also permits various manipulations, including immunodepleting specific proteins, adding purified proteins, and using DNA-coated beads instead of sperm. Importantly, our previous work has also enabled the high-resolution structural analysis of the chromatin-related complexes formed in the Xenopus egg extract. By combining this Xenopus egg extract system with proteomics, genomics, and cryo-EM, we will identify the mechanisms responsible for establishing various types of chromatin regions, such as diffuse interphase chromosomes, compacted M-phase chromosomes, centromeres, and telomeres.
© 2025 Fred Hutchinson Cancer Center, a 501(c)(3) nonprofit organization.