研究実績
2024
Naoki Goto, Kazuma Suke, Nao Yonezawa, Hidenori Nishihara, Tetsuya Handa, Yuko Sato, Tomoya Kujirai, Hitoshi Kurumizaka, Kazuo Yamagata, Hiroshi Kimura
ISWI chromatin remodeling complexes recruit NSD2 and H3K36me2 in pericentromeric heterochromatin Journal Article
In: J Cell Biol, vol. 223, no. 8, 2024, ISSN: 1540-8140.
Abstract | Links | タグ: Kimura G, Kurumizaka G, Yamagata G
@article{pmid38709169,
title = {ISWI chromatin remodeling complexes recruit NSD2 and H3K36me2 in pericentromeric heterochromatin},
author = {Naoki Goto and Kazuma Suke and Nao Yonezawa and Hidenori Nishihara and Tetsuya Handa and Yuko Sato and Tomoya Kujirai and Hitoshi Kurumizaka and Kazuo Yamagata and Hiroshi Kimura},
doi = {10.1083/jcb.202310084},
issn = {1540-8140},
year = {2024},
date = {2024-08-01},
urldate = {2024-08-01},
journal = {J Cell Biol},
volume = {223},
number = {8},
abstract = {Histone H3 lysine36 dimethylation (H3K36me2) is generally distributed in the gene body and euchromatic intergenic regions. However, we found that H3K36me2 is enriched in pericentromeric heterochromatin in some mouse cell lines. We here revealed the mechanism of heterochromatin targeting of H3K36me2. Among several H3K36 methyltransferases, NSD2 was responsible for inducing heterochromatic H3K36me2. Depletion and overexpression analyses of NSD2-associating proteins revealed that NSD2 recruitment to heterochromatin was mediated through the imitation switch (ISWI) chromatin remodeling complexes, such as BAZ1B-SMARCA5 (WICH), which directly binds to AT-rich DNA via a BAZ1B domain-containing AT-hook-like motifs. The abundance and stoichiometry of NSD2, SMARCA5, and BAZ1B could determine the localization of H3K36me2 in different cell types. In mouse embryos, H3K36me2 heterochromatin localization was observed at the two- to four-cell stages, suggesting its physiological relevance.},
keywords = {Kimura G, Kurumizaka G, Yamagata G},
pubstate = {published},
tppubtype = {article}
}
Yuichi Saito, Akihito Harada, Miho Ushijima, Kaori Tanaka, Ryota Higuchi, Akemi Baba, Daisuke Murakami, Stephen L Nutt, Takashi Nakagawa, Yasuyuki Ohkawa, Yoshihiro Baba
Plasma cell differentiation is regulated by the expression of histone variant H3.3 Journal Article
In: Nat Commun, vol. 15, no. 1, pp. 5004, 2024, ISSN: 2041-1723.
Abstract | Links | タグ: Ohkawa G
@article{pmid38902223,
title = {Plasma cell differentiation is regulated by the expression of histone variant H3.3},
author = {Yuichi Saito and Akihito Harada and Miho Ushijima and Kaori Tanaka and Ryota Higuchi and Akemi Baba and Daisuke Murakami and Stephen L Nutt and Takashi Nakagawa and Yasuyuki Ohkawa and Yoshihiro Baba},
doi = {10.1038/s41467-024-49375-x},
issn = {2041-1723},
year = {2024},
date = {2024-06-01},
urldate = {2024-06-01},
journal = {Nat Commun},
volume = {15},
number = {1},
pages = {5004},
abstract = {The differentiation of B cells into plasma cells is associated with substantial transcriptional and epigenetic remodeling. H3.3 histone variant marks active chromatin via replication-independent nucleosome assembly. However, its role in plasma cell development remains elusive. Herein, we show that during plasma cell differentiation, H3.3 is downregulated, and the deposition of H3.3 and chromatin accessibility are dynamically changed. Blockade of H3.3 downregulation by enforced H3.3 expression impairs plasma cell differentiation in an H3.3-specific sequence-dependent manner. Mechanistically, enforced H3.3 expression inhibits the upregulation of plasma cell-associated genes such as Irf4, Prdm1, and Xbp1 and maintains the expression of B cell-associated genes, Pax5, Bach2, and Bcl6. Concomitantly, sustained H3.3 expression prevents the structure of chromatin accessibility characteristic for plasma cells. Our findings suggest that appropriate H3.3 expression and deposition control plasma cell differentiation.},
keywords = {Ohkawa G},
pubstate = {published},
tppubtype = {article}
}
Shiho Makino, Takashi Fukaya
Dynamic modulation of enhancer-promoter and promoter-promoter connectivity in gene regulation Review Article
In: Bioessays, pp. e2400101, 2024, ISSN: 1521-1878.
Abstract | Links | タグ: Fukaya G
@review{pmid38922969,
title = {Dynamic modulation of enhancer-promoter and promoter-promoter connectivity in gene regulation},
author = {Shiho Makino and Takashi Fukaya},
doi = {10.1002/bies.202400101},
issn = {1521-1878},
year = {2024},
date = {2024-06-01},
urldate = {2024-06-01},
journal = {Bioessays},
pages = {e2400101},
abstract = {Enhancers are short segments of regulatory DNA that control when and in which cell-type genes should be turned on in response to a variety of extrinsic and intrinsic signals. At the molecular level, enhancers serve as a genomic scaffold that recruits sequence-specific transcription factors and co-activators to facilitate transcription from linked promoters. However, it remains largely unclear how enhancers communicate with appropriate target promoters in the context of higher-order genome topology. In this review, we discuss recent progress in our understanding of the functional interplay between enhancers, genome topology, and the molecular properties of transcription machineries in gene regulation. We suggest that the activities of transcription hubs are highly regulated through the dynamic rearrangement of enhancer-promoter and promoter-promoter connectivity during animal development.},
keywords = {Fukaya G},
pubstate = {published},
tppubtype = {review}
}
Kosuke Tomimatsu, Takeru Fujii, Ryoma Bise, Kazufumi Hosoda, Yosuke Taniguchi, Hiroshi Ochiai, Hiroaki Ohishi, Kanta Ando, Ryoma Minami, Kaori Tanaka, Taro Tachibana, Seiichi Mori, Akihito Harada, Kazumitsu Maehara, Masao Nagasaki, Seiichi Uchida, Hiroshi Kimura, Masashi Narita, Yasuyuki Ohkawa
Precise immunofluorescence canceling for highly multiplexed imaging to capture specific cell states Journal Article
In: Nat Commun, vol. 15, no. 1, pp. 3657, 2024.
Abstract | Links | タグ: Kimura G, Ochiai G, Ohkawa G
@article{10.1038/s41467-024-47989-9,
title = {Precise immunofluorescence canceling for highly multiplexed imaging to capture specific cell states},
author = {Kosuke Tomimatsu and Takeru Fujii and Ryoma Bise and Kazufumi Hosoda and Yosuke Taniguchi and Hiroshi Ochiai and Hiroaki Ohishi and Kanta Ando and Ryoma Minami and Kaori Tanaka and Taro Tachibana and Seiichi Mori and Akihito Harada and Kazumitsu Maehara and Masao Nagasaki and Seiichi Uchida and Hiroshi Kimura and Masashi Narita and Yasuyuki Ohkawa},
doi = {10.1038/s41467-024-47989-9},
year = {2024},
date = {2024-05-08},
urldate = {2024-05-08},
journal = {Nat Commun},
volume = {15},
number = {1},
pages = {3657},
abstract = {Cell states are regulated by the response of signaling pathways to receptor ligand-binding and intercellular interactions. High-resolution imaging has been attempted to explore the dynamics of these processes and, recently, multiplexed imaging has profiled cell states by achieving a comprehensive acquisition of spatial protein information from cells. However, the specificity of antibodies is still compromised when visualizing activated signals. Here, we develop Precise Emission Canceling Antibodies (PECAbs) that have cleavable fluorescent labeling. PECAbs enable high-specificity sequential imaging using hundreds of antibodies, allowing for reconstruction of the spatiotemporal dynamics of signaling pathways. Additionally, combining this approach with seq-smFISH can effectively classify cells and identify their signal activation states in human tissue. Overall, the PECAb system can serve as a comprehensive platform for analyzing complex cell processes. Multiplexed imaging to study cellular pathways can be hampered by lack of antibody specificity, especially when assessing signal activation. Here, the authors present Precise Emission Canceling Antibodies (PECAbs), which enable high-specificity sequential imaging and the study of signaling pathways.},
keywords = {Kimura G, Ochiai G, Ohkawa G},
pubstate = {published},
tppubtype = {article}
}
Yuko Sato, Maoko Takenoshita, Miku Ueoka, Jun Ueda, Kazuo Yamagata, Hiroshi Kimura
Visualizing histone H4K20me1 in knock-in mice expressing the mCherry-tagged modification-specific intracellular antibody Journal Article
In: Histochem Cell Biol, 2024, ISSN: 1432-119X.
Abstract | Links | タグ: Kimura G, Yamagata G
@article{pmid38762823,
title = {Visualizing histone H4K20me1 in knock-in mice expressing the mCherry-tagged modification-specific intracellular antibody},
author = {Yuko Sato and Maoko Takenoshita and Miku Ueoka and Jun Ueda and Kazuo Yamagata and Hiroshi Kimura},
doi = {10.1007/s00418-024-02296-8},
issn = {1432-119X},
year = {2024},
date = {2024-05-01},
urldate = {2024-05-01},
journal = {Histochem Cell Biol},
abstract = {During development and differentiation, histone modifications dynamically change locally and globally, associated with transcriptional regulation, DNA replication and repair, and chromosome condensation. The level of histone H4 Lys20 monomethylation (H4K20me1) increases during the G2 to M phases of the cell cycle and is enriched in facultative heterochromatin, such as inactive X chromosomes in cycling cells. To track the dynamic changes of H4K20me1 in living cells, we have developed a genetically encoded modification-specific intracellular antibody (mintbody) probe that specifically binds to the modification. Here, we report the generation of knock-in mice in which the coding sequence of the mCherry-tagged version of the H4K20me1-mintbody is inserted into the Rosa26 locus. The knock-in mice, which ubiquitously expressed the H4K20me1-mintbody, developed normally and were fertile, indicating that the expression of the probe does not disturb the cell growth, development, or differentiation. Various tissues isolated from the knock-in mice exhibited nuclear fluorescence without the need for fixation. The H4K20me1-mintbody was enriched in inactive X chromosomes in developing embryos and in XY bodies during spermatogenesis. The knock-in mice will be useful for the histochemical analysis of H4K20me1 in any cell types.},
keywords = {Kimura G, Yamagata G},
pubstate = {published},
tppubtype = {article}
}