Figure 1: RIKEN researchers have succeeded in reconstituting long stretches of chromatin arrays. In this atomic force microscopy image, the reconstituted chromatin array contains about 98 nucleosomes. © 2026 RIKEN Nonequilibrium Physics of Living Matter Laboratory
Certain epigenetic modifications can directly control how genetic material is packed in the nucleus, RIKEN researchers have shown1. This has important implications for our understanding of how genes are expressed in different cell types.
Virtually every cell in your body contains a full copy of your DNA. But various factors determine which genes are expressed in each cell type, imparting it with its unique characteristics.
One of the most important of these factors is the three-dimensional organization of DNA and proteins in structures known as chromatins inside the nucleus.
Working at the intersection of biochemistry and biophysics, Yohsuke Fukai and Kyogo Kawaguchi, both of the RIKEN Nonequilibrium Physics of Living Matter Laboratory, are interested in developing a physical model of how chemical modifications affect the structure of chromatins.
"The genome structure is thought to play an important role in the expression of genes specific to a given cell type," says Fukai. "Developing a physical model is important because it provides insights into how these processes occur."
One challenge in determining how epigenetic modifications shape chromatin structure on a gene scale has the difficulty in reconstituting sufficiently long arrays of chromatin in the lab.
Fukai, Kawaguchi and co-workers have overcome this problem by developing a novel way to reconstitute chromatin arrays in a dish.
"Rather than using a long DNA array to reconstitute the chromatin, we adopted a two-step approach in which we first reconstituted the chromatin using short DNA and then joined eight of them together," explains Kawaguichi. "The DNA has carefully designed sticky ends so that they joined together with a defined order in one-pot reaction."
This method allowed the team to probe the relationship between epigenetic patterns and chromatin structure at a larger scale than previous studies.
They found that histone acetylation-an epigenetic modification involving the addition of an acetyl group to specific amino acids found in chromatin proteins known as histones-directly controls chromatin architecture.
The study also highlights the importance of hydrodynamic interactions in chromatin dynamics, suggesting that these effects are significant in cellular processes.
Since being published in November 2025, the paper has been downloaded more than 6,700 times, indicating a high amount of interest in it. Other teams might want to use the same technique in their research, Kawaguchi thinks.
The team now plans to investigate the effects of various modifications and proteins that bind to nucleosomes. "Our ultimate goal is to build a robust physical model of chromatin and to understand the biochemical mechanisms behind its organization in the nucleus," says Fukai.
