The human genome is about two meters long, yet it is folded inside a cell nucleus only about 10 micrometers in diameter. To fit into this tiny space, DNA is wrapped around histone proteins to form nucleosomes, which are further organized into chromatin. For decades, chromatin has often been described in two simple forms: euchromatin, which is active, open (Figure A), and accessible, and heterochromatin, which is more compact and repressed.
However, a new study from an international team led by Professor Kazuhiro Maeshima at the National Institute of Genetics, ROIS (Research Organization of Information and Systems) and SOKENDAI has challenged this simple textbook view. They have demonstrated that euchromatin in living human cells is not merely open and loose, but forms dynamic condensed domains (Figure B). This domain organization helps to prevent mixing of neighboring domains. The international team has further found that cohesin, a ring-shaped protein complex best known for organizing genome architecture, prevents local mixing between these condensed euchromatic domains for proper gene regulation in living human cells. The study was published in Nature Genetics on September 8, 2026.
DOI: 10.1038/s41588-026-02736-2
The cohesin complex is widely known for forming chromatin loops and contributing to genome organization. In this study, the researchers asked whether cohesin also controls the physical properties of euchromatic domains at the level of individual nucleosomes.
To address this, the team combined single-nucleosome imaging and tracking in living human cells with super-resolution 3D-structured illumination microscopy (3D-SIM). Single-nucleosome imaging allowed the researchers to follow the movement of individual nucleosomes, while 3D-SIM enabled them to visualize the euchromatic domains at about 100 nm resolution.
The researchers found that removing cohesin increased the mobility of nucleosomes within euchromatic domains, making them more fluid-like (Figure C). Surprisingly, this increase in fluidity occurred without altering overall chromatin compaction. In other words, euchromatic domains did not simply open up or decondense globally. Instead, cohesin loss caused neighboring condensed domains to mix locally.
"This was an important point for us," said Maeshima. "Cohesin loss did not simply make euchromatin open. Rather, it made condensed euchromatic domains more fluid and led to local domain mixing."
The team further showed that this local mixing has functional consequences. Euchromatic domains are not only structural units; they also help separate transcriptional environments (transcriptional insulation). When cohesin was removed, local domain mixing was accompanied by weakened transcriptional insulation: genes in neighboring domains became more likely to switch on together (Figure C).
"Our results suggest that cohesin acts like a constraint that keeps active chromatin domains from mixing too much," said Shimazoe and Iida. "This provides a physical explanation for how cohesin contributes to transcriptional insulation in living cells."
The study supports a revised view of euchromatin. Rather than being simply open and accessible, euchromatin can form condensed, dynamic domains whose local mixing is actively controlled, while still allowing genes to be accessed.
"Euchromatin is often described as open chromatin," said Shimazoe and Iida. "But our work suggests that euchromatin is better understood as forming condensed, dynamic, and functionally insulated domains. Cohesin helps maintain this organization."
The researchers hope that this new physical view of euchromatin will deepen our understanding of gene regulation, genome organization, development, and disease. Because cohesin dysfunction is linked to developmental disorders and cancer, understanding how cohesin controls chromatin domain behavior may also provide new insight into how genome regulation fails in disease.
About National Institute of Genetics
The National Institute of Genetics (NIG) was established to carry out broad and comprehensive research in genetics. NIG contributes to the development of academic research as one of the inter-university research institutes constituting the Research Organization of Information and Systems (ROIS).
About the Research Organization of Information and Systems
ROIS is a parent organization of four national institutes: the National Institute of Polar Research, the National Institute of Informatics, the Institute of Statistical Mathematics, and the National Institute of Genetics. ROIS promotes integrated, cutting-edge research that goes beyond the barriers of these institutions.
