生きた細胞内で「ユークロマチン」と「ヘテロクロマチン」のふるまいを見分ける新技術を開発

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2025-03-31 国立遺伝学研究所

国立遺伝学研究所の研究チームは、生きた細胞内で「ユークロマチン」と「ヘテロクロマチン」を識別する新技術を開発しました。 この手法では、特定の蛍光タンパク質を用いて、ユークロマチンとヘテロクロマチンの動態をリアルタイムで観察することが可能です。これにより、遺伝子発現の制御機構やクロマチン構造の変化を詳細に解析でき、将来的にはエピジェネティクス研究や疾患の理解に貢献することが期待されます。

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複製依存的ヒストン標識が生きたヒト細胞におけるユークロマチン/ヘテロクロマチンの物理的性質を解明する Replication-dependent histone labeling dissects the physical properties of euchromatin/heterochromatin in living human cells

Katsuhiko Minami, Kako Nakazato, Satoru Ide, Kazunari Kaizu, […], and Kazuhiro Maeshima
Science Advances  Published:28 Mar 2025
DOI:https://doi.org/10.1126/sciadv.adu8400

生きた細胞内で「ユークロマチン」と「ヘテロクロマチン」のふるまいを見分ける新技術を開発

Abstract

A string of nucleosomes, where genomic DNA is wrapped around histones, is organized in the cell as chromatin, ranging from euchromatin to heterochromatin, with distinct genome functions. Understanding physical differences between euchromatin and heterochromatin is crucial, yet specific labeling methods in living cells remain limited. Here, we have developed replication-dependent histone (Repli-Histo) labeling to mark nucleosomes in euchromatin and heterochromatin based on DNA replication timing. Using this approach, we investigated local nucleosome motion in the four known chromatin classes, from euchromatin to heterochromatin, of living human and mouse cells. The more euchromatic (earlier-replicated) and more heterochromatic (later-replicated) regions exhibit greater and lesser nucleosome motions, respectively. Notably, the motion profile in each chromatin class persists throughout interphase. Genome chromatin is essentially replicated from regions with greater nucleosome motions, although the replication timing is perturbed. Our findings, combined with computational modeling, suggest that earlier-replicated regions have more accessibility, and local chromatin motion can be a major determinant of genome-wide replication timing.

生物工学一般
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