DATE2025.11.20 #Press Releases

Designing and Reconstituting Gene-Scale Chromatin

-A New Foundation for Genome Physics Unveiling the Principles of 3D DNA Architecture-

Summary

A research team consisting of Yosuke Fukai (RIKEN BDR; at the time of research), Kyogo Kawaguchi (RIKEN Hakubi Team Leader at the time; currently Chief Scientist at the RIKEN Pioneering Research Institute and Associate Professor at the University of Tokyo), Masaaki Wakamori (RIKEN BDR Epigenetic Regulation Research Team; at the time), Takashi Umehara (RIKEN BDR; at the time, now Professor at Ritsumeikan University), Tomoya Kujirai (Lecturer, Institute for Quantitative Biosciences, The University of Tokyo), and Hitoshi Kurumizaka (Professor, The University of Tokyo) has developed a new in vitro method to reconstitute eukaryotic chromatin using designed histone modification patterns. This technique enabled the first structural and dynamic analysis of reconstituted chromatin at the gene scale, corresponding to approximately 20,000 base pairs.

This research provides a quantitative framework for elucidating the principles underlying the formation of the three-dimensional genome architecture that governs cell fate. In the future, it is expected to contribute to the development of technologies capable of predicting and controlling chromatin structure, gene expression, and cellular functions based on histone modification patterns.

In eukaryotes, the genome is organized in the nucleus as chromatin, whose fundamental unit is the nucleosome—DNA wrapped around a histone protein octamer. These nucleosomes are linked like beads on a string. The three-dimensional structure of chromatin changes in correlation with post-translational modifications such as histone acetylation, and these structural changes are involved in gene expression and cellular differentiation.

The collaborative research team developed a method to synthesize chromatin strands of gene-scale length (“long-chain chromatin”) under precisely controlled modification patterns. Using this experimental system, they directly demonstrated for the first time—through single-molecule observation and other techniques—that the pattern of nucleosome–nucleosome contact frequencies and the dynamic fluctuations of chromatin structure vary substantially depending on the pattern of histone acetylation along the chromatin.

The results of this study were published in the online edition of Science Advances on November 19 (Japan time: November 20).

Figure：Reconstituted “long-chain chromatin” consisting of 96 nucleosomes arranged like beads on a string

Links

RIKEN, Institute for Quantitative Life Sciences, Ritsumeikan University, Japan Science and Technology Agency

Journals

Journal name	Science Advances
Title of paper	Gene-scale in vitro reconstitution reveals histone acetylation directly controls chromatin architecture