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Peer-reviewedCC BYNature Genetics

Cohesin prevents local mixing of condensed euchromatic domains in living human cells

  • Masa A. Shimazoe1,2
  • Shiori Iida3,1,2
  • Katsuhiko Minami4,1,2
  • Koichi Higashi5,2
  • Sachiko Tamura1
  • Yoshiaki Kobayashi6
  • Shin Fujishiro7
  • Le Xiong8
  • Kako Nakazato1,2
  • S. S. Ashwin9
  • Tomoko Nishiyama10
  • Yu Nagata1,2
10 more authors
  • Masato T. Kanemaki11,2,12
  • Akane Kawaguchi2,13
  • Yasuyuki Ohkawa14
  • Lothar Schermelleh15
  • Atsushi Toyoda16
  • Liangqi Xie8
  • Ken Kurokawa5,2
  • Hiroshi Ochiai6
  • Masaki Sasai17,7
  • Kazuhiro Maeshima18,19
19 affiliations
  1. 1Genome Dynamics Laboratory, National Institute of Genetics, ROIS, Mishima, Japan
  2. 2Graduate Institute for Advanced Studies, Graduate University for Advanced Studies (SOKENDAI), Mishima, Japan
  3. 3Department of Cell and Tissue Dynamics, Max Planck Institute for Molecular Biomedicine, Münster, Germany
  4. 4Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA, USA
  5. 5Genome Evolution Laboratory, National Institute of Genetics, Mishima, Japan
  6. 6Division of Gene Expression Dynamics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan
  7. 7Fukui Institute for Fundamental Chemistry, Kyoto University, Kyoto, Japan
  8. 8Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
  9. 9Department of Physics, Gandhi Institute of Technology and Management (GITAM) University, Bengaluru, India
  10. 10Division of Biological Sciences, Graduate School of Science, Kyoto University, Kyoto, Japan
  11. 11Department of Biological Science, Graduate School of Science, The University of Tokyo, Tokyo, Japan
  12. 12Molecular Cell Engineering Laboratory, National Institute of Genetics, ROIS, Mishima, Japan
  13. 13Laboratory for Molecular Life History, National Institute of Genetics, ROIS, Mishima, Japan
  14. 14Division of Transcriptomics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan
  15. 15Department of Biochemistry, University of Oxford, Oxford, UK
  16. 16Comparative Genomics Laboratory, National Institute of Genetics, ROIS, Mishima, Japan
  17. 17Department of Complex Systems Science, Nagoya University, Nagoya, Japan
  18. 18Genome Dynamics Laboratory, National Institute of Genetics, ROIS, Mishima, Japan. [email protected]
  19. 19Graduate Institute for Advanced Studies, Graduate University for Advanced Studies (SOKENDAI), Mishima, Japan. [email protected]
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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. To address this question, we combined single-nucleosome imaging/tracking and super-resolution 3D-structured illumination microscopy (3D-SIM) with euchromatin-specific labeling of histone 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 textbook 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 fluidity within these domains without altering their overall compaction, leading to local mixing of domains and compromising transcriptional insulation. These findings uncover an unexpected physical role of cohesin in maintaining the integrity of condensed euchromatic domains and ensuring proper higher-order regulation of gene expression.

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Cite

BibTeXRIS
BibTeX
@article{shimazoe2026cohesin,
  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},
  journal = {Nature Genetics},
  year = {2026},
  month = sep,
  doi = {10.1038/s41588-026-02736-2},
  url = {https://doi.org/10.1038/s41588-026-02736-2},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Cohesin prevents local mixing of condensed euchromatic domains in living human cells
AU  - Masa A. Shimazoe
AU  - Shiori Iida
AU  - Katsuhiko Minami
AU  - Koichi Higashi
AU  - Sachiko Tamura
AU  - Yoshiaki Kobayashi
AU  - Shin Fujishiro
AU  - Le Xiong
AU  - Kako Nakazato
AU  - S. S. Ashwin
AU  - Tomoko Nishiyama
AU  - Yu Nagata
AU  - Masato T. Kanemaki
AU  - Akane Kawaguchi
AU  - Yasuyuki Ohkawa
AU  - Lothar Schermelleh
AU  - Atsushi Toyoda
AU  - Liangqi Xie
AU  - Ken Kurokawa
AU  - Hiroshi Ochiai
AU  - Masaki Sasai
AU  - Kazuhiro Maeshima
PY  - 2026
DA  - 2026/09/01
JO  - Nature Genetics
DO  - 10.1038/s41588-026-02736-2
UR  - https://doi.org/10.1038/s41588-026-02736-2
AB  - 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. To address this question, we combined single-nucleosome imaging/tracking and super-resolution 3D-structured illumination microscopy (3D-SIM) with euchromatin-specific labeling of histone 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 textbook 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 fluidity within these domains without altering their overall compaction, leading to local mixing of domains and compromising transcriptional insulation. These findings uncover an unexpected physical role of cohesin in maintaining the integrity of condensed euchromatic domains and ensuring proper higher-order regulation of gene expression.
SN  - 1061-4036
SN  - 1546-1718
ER  -