Authors
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
Published in
Nature genetics. Volume 58. Issue 9. Pages 2335-2349. Epub Sep 08, 2026.
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.
PMID:
42711428
Bibliographic data and abstract were imported from PubMed on 09 Sep 2026.
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