video: Movie 1: Movement of single nucleosomes in living human cells. The movie shows nucleosome fluctuations in euchromatin (left), where gene expression is active, and in heterochromatin (right), where gene expression is repressed. Each dot represents an individual nucleosome.
Credit: Katsuhiko Minami & Kazuhiro Maeshima, National Institute of Genetics, ROIS
A team led by Professor Kazuhiro Maeshima of the National Institute of Genetics (ROIS) and SOKENDAI in Japan has developed a method to visualize different types of chromatin and reveal their distinct physical properties. They published their approach and findings on March 28th in Science Advances.
DOI： https://doi.org/10.1126/sciadv.adu8400
Inside every human cell, 2 meters of DNA must be tightly packed into a tiny nucleus. This DNA is wrapped around proteins to form chromatin, which exists in two main forms: Euchromatin, where genes are active, and heterochromatin, where gene activity is suppressed.
"How these two types of chromatin are organized and behave inside living cells is still not well understood," says Katsuhiko Minami, the first author of this study. "Until now, we lacked a way to specifically label euchromatin and heterochromatin in live cells."
To solve this problem, the researchers developed "Repli-Histo labeling," a breakthrough technique that allows them to visualize euchromatin and heterochromatin in living cells (Movie). Their findings show that euchromatin is more flexible and dynamic, while heterochromatin is more rigid and static (Fig. 1). This suggests that euchromatin behaves more like a liquid, allowing proteins and other molecules to move in and interact with genes. On the other hand, heterochromatin acts more like a gel, making it harder for molecules to enter. This key difference could affect how genes are accessed and used by the cell to regulate important processes like gene expression and DNA replication (Fig. 1).
"These differences in chromatin behavior are crucial for understanding how cells control which genes are turned on or off," explains Kako Nakazato, co-author of the study. "If chromatin is too rigid or too loose, it could lead to problems in how our genes function."
This discovery changes how scientists think about chromatin. Instead of being a static structure, chromatin is constantly moving, influencing how genes are read and used by the cell.
"In simple terms, chromatin isn't just a container for genome information—it plays an active role in regulating gene function," says Minami. "Our technique gives us a new way to study these movements and how they affect important cellular processes like gene expression and DNA replication."
The researchers plan to use Repli-Histo labeling to create a chromatin behavior atlas—a map showing how different factors, such as epigenetic modifications, influence chromatin’s movement and flexibility.
"Our ultimate goal is to understand how the genome, stored in 2 meters of DNA, is efficiently managed inside a tiny nucleus," says Maeshima. "This research could help us better understand not only normal gene function but also what goes wrong in diseases like cancer."
The study was led by corresponding author Kazuhiro Maeshima, Katsuhiko Minami, Kako Nakazato, Satoru Ide, Koichi Higashi, Sachiko Tamura, Atsushi Toyoda, and Ken Kurokawa from the National Institute of Genetics (ROIS); Kazunari Kaizu and Koichi Takahashi from RIKEN Center for Biosystems Dynamics Research. Minami, Nakazato, Ide, Higashi, Kurokawa, and Maeshima also belong to SOKENDAI; Kaizu also belongs to ExCELLS (National Institutes of Natural Sciences). Ide is currently with the Tokyo Metropolitan Institute of Medical Science.
This work was supported by the JSPS and MEXT KAKENHI grants JP20H05936, JP21H02453, JP23K17398, JP22H04925 (PAGS), JP24H00061, 21H02535, JP22H05606, JP23KJ0998, JST SPRING grant JPMJSP2104, and Takeda Science Foundation.
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About National Institute of Genetics (NIG)
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)
ROIS is a parent organization of four national institutes (National Institute of Polar Research, National Institute of Informatics, the Institute of Statistical Mathematics and National Institute of Genetics) and the Joint Support-Center for Data Science Research. It is ROIS's mission to promote integrated, cutting-edge research that goes beyond the barriers of these institutions, in addition to facilitating their research activities, as members of inter-university research institutes.
Journal
Science Advances