研究実績
2026
4.
Masa A. Shimazoe, Shiori Iida, Katsuhiko Minami, Koichi Higashi, Sachiko Tamura, Yoshiaki Kobayashi, Shin Fujishiro, Le Xiong, Kako Nakazato, S. S. Ashwin, Tomoko Nishiyama, Yu Nagata, Masato T. Kanemaki, Akane Kawaguchi, Yasuyuki Ohkawa, Lothar Schermelleh, Atsushi Toyoda, Liangqi Xie, Ken Kurokawa, Hiroshi Ochiai, Masaki Sasai, Kazuhiro Maeshima
Cohesin prevents local mixing of condensed euchromatic domains in living human cells Journal Article
In: Nature Genetics, vol. 58, no. 9, pp. 2335–2349, 2026, ISSN: 1546-1718.
Abstract | Links | タグ: Kawaguchi G, Nishiyama G, Ochiai G, Ohkawa G
@article{Shimazoe2026,
title = {Cohesin prevents local mixing of condensed euchromatic domains in living human cells},
author = {Masa A. Shimazoe and Shiori Iida and Katsuhiko Minami and Koichi Higashi and Sachiko Tamura and Yoshiaki Kobayashi and Shin Fujishiro and Le Xiong and Kako Nakazato and S. S. Ashwin and Tomoko Nishiyama and Yu Nagata and Masato T. Kanemaki and Akane Kawaguchi and Yasuyuki Ohkawa and Lothar Schermelleh and Atsushi Toyoda and Liangqi Xie and Ken Kurokawa and Hiroshi Ochiai and Masaki Sasai and Kazuhiro Maeshima},
url = {https://www.nature.com/articles/s41588-026-02736-2},
doi = {10.1038/s41588-026-02736-2},
issn = {1546-1718},
year = {2026},
date = {2026-09-08},
urldate = {2026-09-08},
journal = {Nature Genetics},
volume = {58},
number = {9},
pages = {2335--2349},
publisher = {Springer Science and Business Media LLC},
abstract = {The human genome is folded into chromatin loops by the cohesin complex, forming functional chromatin domains that underlie transcription and DNA replication/repair. However, how cohesin organizes these domains in living cells, especially in active euchromatin, remains elusive. Here, to address this question, we combined single-nucleosome imaging/tracking and super-resolution three-dimensional structured illumination microscopy with euchromatin-specific labeling of histone variant H3.3. Using this nanoscopic approach, we revealed that euchromatin forms condensed domains that are constrained by cohesin-mediated loops. This organization refines the classical view of euchromatin as largely open, in line with emerging evidence. Transcription machinery appears to be located near the condensed domain surfaces/borders. Cohesin loss increased nucleosome-level fluidity within these domains without altering their overall compaction, leading to local mixing of domains and compromising transcriptional insulation. These findings suggest a physical role of cohesin in maintaining the integrity of condensed euchromatic domains and ensuring proper higher-order regulation of gene expression.},
keywords = {Kawaguchi G, Nishiyama G, Ochiai G, Ohkawa G},
pubstate = {published},
tppubtype = {article}
}
The human genome is folded into chromatin loops by the cohesin complex, forming functional chromatin domains that underlie transcription and DNA replication/repair. However, how cohesin organizes these domains in living cells, especially in active euchromatin, remains elusive. Here, to address this question, we combined single-nucleosome imaging/tracking and super-resolution three-dimensional structured illumination microscopy with euchromatin-specific labeling of histone variant H3.3. Using this nanoscopic approach, we revealed that euchromatin forms condensed domains that are constrained by cohesin-mediated loops. This organization refines the classical view of euchromatin as largely open, in line with emerging evidence. Transcription machinery appears to be located near the condensed domain surfaces/borders. Cohesin loss increased nucleosome-level fluidity within these domains without altering their overall compaction, leading to local mixing of domains and compromising transcriptional insulation. These findings suggest a physical role of cohesin in maintaining the integrity of condensed euchromatic domains and ensuring proper higher-order regulation of gene expression.
3.
Xiaohui Gao, Chaebeen Ko, Yuanchao Dong, Takeru Fujii, Satoshi Uchino, Yoshiaki Kobayashi, Akihito Harada, Hiroaki Ohishi, Yasuyuki Ohkawa, Hiroshi Kimura, Hiroshi Ochiai
Minute-scale coupling of chromatin marks and transcriptional bursts Journal Article
In: bioRxiv, 2026.
Abstract | Links | タグ: Kimura G, Ochiai G, Ohkawa G
@article{Gao2026.02.08.704500,
title = {Minute-scale coupling of chromatin marks and transcriptional bursts},
author = {Xiaohui Gao and Chaebeen Ko and Yuanchao Dong and Takeru Fujii and Satoshi Uchino and Yoshiaki Kobayashi and Akihito Harada and Hiroaki Ohishi and Yasuyuki Ohkawa and Hiroshi Kimura and Hiroshi Ochiai},
url = {https://www.biorxiv.org/content/early/2026/02/10/2026.02.08.704500},
doi = {10.64898/2026.02.08.704500},
year = {2026},
date = {2026-02-10},
urldate = {2026-01-01},
journal = {bioRxiv},
publisher = {Cold Spring Harbor Laboratory},
abstract = {Histone modifications are often described as stable epigenetic marks that contribute to maintaining gene-expression programs during development and environmental responses. However, transcription of many genes is intermittent, switching between transcriptionally active and inactive episodes within minutes. Whether chromatin marks around individual genes change on these rapid timescales remains unclear. Here we show that local chromatin modification signals around endogenous genes in mouse embryonic stem cells fluctuate reversibly with transcriptional state, using live imaging of individual genes together with fluorescent probes that report histone modifications. Activation-associated acetylation and methylation marks increased in association with transcriptional activation and decreased with inactivation, whereas a Polycomb-associated repressive mark behaved oppositely. Transcriptional coactivators and both histone acetyltransferase and deacetylase complexes were enriched during transcriptionally active state, consistent with opposing enzymatic activities shaping local acetylation levels. Inhibiting histone deacetylases altered the durations of active and inactive events, supporting a role for deacetylation in regulating transcriptional state transitions. Thus, histone modifications undergo reversible, minute-scale changes coupled to transcriptional activity. This framework helps explain how stochastic transcriptional bursts can occur with stable gene regulation over longer timescales.},
keywords = {Kimura G, Ochiai G, Ohkawa G},
pubstate = {published},
tppubtype = {article}
}
Histone modifications are often described as stable epigenetic marks that contribute to maintaining gene-expression programs during development and environmental responses. However, transcription of many genes is intermittent, switching between transcriptionally active and inactive episodes within minutes. Whether chromatin marks around individual genes change on these rapid timescales remains unclear. Here we show that local chromatin modification signals around endogenous genes in mouse embryonic stem cells fluctuate reversibly with transcriptional state, using live imaging of individual genes together with fluorescent probes that report histone modifications. Activation-associated acetylation and methylation marks increased in association with transcriptional activation and decreased with inactivation, whereas a Polycomb-associated repressive mark behaved oppositely. Transcriptional coactivators and both histone acetyltransferase and deacetylase complexes were enriched during transcriptionally active state, consistent with opposing enzymatic activities shaping local acetylation levels. Inhibiting histone deacetylases altered the durations of active and inactive events, supporting a role for deacetylation in regulating transcriptional state transitions. Thus, histone modifications undergo reversible, minute-scale changes coupled to transcriptional activity. This framework helps explain how stochastic transcriptional bursts can occur with stable gene regulation over longer timescales.
2024
2.
Hiroaki Ohishi, Soya Shinkai, Hitoshi Owada, Takeru Fujii, Kazufumi Hosoda, Shuichi Onami, Takashi Yamamoto, Yasuyuki Ohkawa, Hiroshi Ochiai
Transcription-coupled changes in genomic region proximities during transcriptional bursting Journal Article
In: Sci. Adv., vol. 10, no. 49, 2024, ISSN: 2375-2548.
Abstract | Links | タグ: Ochiai G, Ohkawa G
@article{Ohishi2024,
title = {Transcription-coupled changes in genomic region proximities during transcriptional bursting},
author = {Hiroaki Ohishi and Soya Shinkai and Hitoshi Owada and Takeru Fujii and Kazufumi Hosoda and Shuichi Onami and Takashi Yamamoto and Yasuyuki Ohkawa and Hiroshi Ochiai},
doi = {10.1126/sciadv.adn0020},
issn = {2375-2548},
year = {2024},
date = {2024-12-06},
urldate = {2024-12-06},
journal = {Sci. Adv.},
volume = {10},
number = {49},
publisher = {American Association for the Advancement of Science (AAAS)},
abstract = {<jats:p>The orchestration of our genes heavily relies on coordinated communication between enhancers and promoters, yet the mechanisms behind this dynamic interplay during active transcription remain unclear. Here, we investigated enhancer-promoter (E-P) interactions in relation to transcriptional bursting in mouse embryonic stem cells using sequential DNA/RNA/immunofluorescence–fluorescence in situ hybridization analyses. Our data reveal that the active state of specific genes is characterized by specific proximities between different genomic regions and the accumulation of transcriptional regulatory factors. Mathematical simulations suggest that an increase in local viscosity could potentially contribute to stabilizing the duration of these E-P proximities. Our study provides insights into the association among E-P proximity, protein accumulation, and transcriptional dynamics, paving the way for a more nuanced understanding of gene-specific regulatory mechanisms.</jats:p>},
keywords = {Ochiai G, Ohkawa G},
pubstate = {published},
tppubtype = {article}
}
<jats:p>The orchestration of our genes heavily relies on coordinated communication between enhancers and promoters, yet the mechanisms behind this dynamic interplay during active transcription remain unclear. Here, we investigated enhancer-promoter (E-P) interactions in relation to transcriptional bursting in mouse embryonic stem cells using sequential DNA/RNA/immunofluorescence–fluorescence in situ hybridization analyses. Our data reveal that the active state of specific genes is characterized by specific proximities between different genomic regions and the accumulation of transcriptional regulatory factors. Mathematical simulations suggest that an increase in local viscosity could potentially contribute to stabilizing the duration of these E-P proximities. Our study provides insights into the association among E-P proximity, protein accumulation, and transcriptional dynamics, paving the way for a more nuanced understanding of gene-specific regulatory mechanisms.</jats:p>
1.
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}
}
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.
