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

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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Publication Details

Journal
Nature Genetics
Published
2026-09-08
DOI
https://doi.org/10.1038/s41588-026-02736-2
Citations
7
Primary Topic
Single-cell and spatial transcriptomics
Type
article
Field-Weighted Citation Impact
11.41

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article

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

Masa A. Shimazoe, Masaki Sasai, Tomoko Nishiyama, Masato T. Kanemaki et al.
7 citations
Nature Genetics
Single-cell and spatial transcriptomics
11.41
article

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

Masa A. Shimazoe, Masaki Sasai, Tomoko Nishiyama, Masato T. Kanemaki, Atsushi Toyoda, Kazuhiro Maeshima, Shiori Iida, Sarah Ashwin, Koichi Higashi, Sachiko Tamura, Katsuhiko Minami, Lothar Schermelleh, Ken Kurokawa
article en
7 citations

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.

Nature GeneticsVol. 58(9)
National Institute of Genetics (JP), Kyushu University (JP), Harvard University (US), The Graduate University for Advanced Studies, SOKENDAI (JP), Kyoto University (JP), Cleveland Clinic Lerner College of Medicine (US), University of Oxford (GB), Max Planck Institute for Molecular Biomedicine (DE), Nagoya University (JP), The University of Tokyo (JP), GITAM University (IN)
American Cancer Society, Research Organization of Information and Systems, Japan Society for the Promotion of Science
Openalex Percentile: Top 2%
Single-cell and spatial transcriptomics
11.41
DOIOpen Access PDFOpenAlex
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