DNA鎖を光で曲げ、ゲノムを研究する新しい方法を発見(Researchers bend DNA strands with light, revealing a new way to study the genome)

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2024-09-09 プリンストン大学

プリンストン大学の研究チームは、光を使ってDNA鎖を曲げ、ゲノムの物理的性質を調べる新しい技術を開発しました。研究者は、液滴を使ってDNAの特定の部分を動かし、2つの遺伝子を物理的に接近させることに成功しました。この技術は、遺伝子の発現や制御を新たに理解する手段として期待され、DNAの物理的な操作によって、遺伝子の発現がどのように変わるかを調べることができます。

<関連情報>

凝縮界面力によるDNA座位の再配置とクロマチン粘弾性のプローブ Condensate interfacial forces reposition DNA loci and probe chromatin viscoelasticity

Amy R. Strom, Yoonji Kim, Hongbo Zhao ,… , Andrej Košmrlj, Cornelis Storm,Clifford P. Brangwynne
Cell  Published:August 20, 2024
DOI:https://doi.org/10.1016/j.cell.2024.07.034

Graphical abstract

DNA鎖を光で曲げ、ゲノムを研究する新しい方法を発見(Researchers bend DNA strands with light, revealing a new way to study the genome)

Highlights

  • VECTOR enables rapid, precise genome reorganization through condensate capillarity
  • Engineered condensate interfaces exert force on programmable target loci
  • DNA loci exhibit significant viscoelastic heterogeneity across nuclear positions
  • Native condensates are likely sites of force generation without ATP-driven motors

Summary

Biomolecular condensates assemble in living cells through phase separation and related phase transitions. An underappreciated feature of these dynamic molecular assemblies is that they form interfaces with other cellular structures, including membranes, cytoskeleton, DNA and RNA, and other membraneless compartments. These interfaces are expected to give rise to capillary forces, but there are few ways of quantifying and harnessing these forces in living cells. Here, we introduce viscoelastic chromatin tethering and organization (VECTOR), which uses light-inducible biomolecular condensates to generate capillary forces at targeted DNA loci. VECTOR can be utilized to programmably reposition genomic loci on a timescale of seconds to minutes, quantitatively revealing local heterogeneity in the viscoelastic material properties of chromatin. These synthetic condensates are built from components that naturally form liquid-like structures in living cells, highlighting the potential role for native condensates to generate forces and do work to reorganize the genome and impact chromatin architecture.

細胞遺伝子工学
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