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活细胞内基因组 locus 的微操作揭示了间期染色质的力学性质。

Live-cell micromanipulation of a genomic locus reveals interphase chromatin mechanics.

机构信息

Institut Curie, PSL Research University, Sorbonne Université, CNRS UMR3664, Laboratoire Dynamique du Noyau, 75005 Paris, France.

Institut Curie, PSL Research University, Sorbonne Université, CNRS UMR168, Laboratoire Physico Chimie Curie, 75005 Paris, France.

出版信息

Science. 2022 Jul 29;377(6605):489-495. doi: 10.1126/science.abi9810. Epub 2022 Jul 28.


DOI:10.1126/science.abi9810
PMID:
Abstract

Our understanding of the physical principles organizing the genome in the nucleus is limited by the lack of tools to directly exert and measure forces on interphase chromosomes in vivo and probe their material nature. Here, we introduce an approach to actively manipulate a genomic locus using controlled magnetic forces inside the nucleus of a living human cell. We observed viscoelastic displacements over micrometers within minutes in response to near-piconewton forces, which are consistent with a Rouse polymer model. Our results highlight the fluidity of chromatin, with a moderate contribution of the surrounding material, revealing minor roles for cross-links and topological effects and challenging the view that interphase chromatin is a gel-like material. Our technology opens avenues for future research in areas from chromosome mechanics to genome functions.

摘要

我们对基因组在核内的物理原理的理解受到限制,因为缺乏直接施加和测量活体间期染色体力的工具,并探测其物质本质。在这里,我们引入了一种在活的人类细胞核内使用受控磁力主动操纵基因组位点的方法。我们观察到在皮牛顿力的作用下,几分钟内就会发生微米级的粘弹性位移,这与罗瑟高分子模型一致。我们的结果突出了染色质的流动性,周围物质的贡献适中,表明交联和拓扑效应的作用较小,挑战了间期染色质是凝胶样物质的观点。我们的技术为从染色体力学到基因组功能等领域的未来研究开辟了道路。

相似文献

[1]
Live-cell micromanipulation of a genomic locus reveals interphase chromatin mechanics.

Science. 2022-7-29

[2]
Simulation of different three-dimensional polymer models of interphase chromosomes compared to experiments-an evaluation and review framework of the 3D genome organization.

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[3]
Multi-contact 3C reveals that the human genome during interphase is largely not entangled.

Nat Struct Mol Biol. 2020-12

[4]
Mini review: form and function in the human interphase chromosome.

Cytogenet Cell Genet. 2000

[5]
Genomics tools for unraveling chromosome architecture.

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[6]
A proposed unified interphase nucleus chromosome structure: Preliminary preponderance of evidence.

Proc Natl Acad Sci U S A. 2022-6-28

[7]
Simulating Dynamic Chromosome Compaction: Methods for Bridging In Silico to In Vivo.

Methods Mol Biol. 2022

[8]
Single-chromosome dynamics reveals locus-dependent dynamics and chromosome territory orientation.

J Cell Sci. 2023-2-15

[9]
Chromatin Domains: The Unit of Chromosome Organization.

Mol Cell. 2016-6-2

[10]
SAP-like domain in nucleolar spindle associated protein mediates mitotic chromosome loading as well as interphase chromatin interaction.

Biochem Biophys Res Commun. 2011-7-18

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[1]
Robotic micromanipulation for patterned and complex organoid biofabrication.

Sci Adv. 2025-9-5

[2]
Heterogeneity as a feature: unraveling chromatin's role in nuclear mechanics.

Nucleus. 2025-12

[3]
Enhancer Placement Impacts Transcriptional Dynamics in Embryos.

bioRxiv. 2025-8-16

[4]
Peripheral heterochromatin tethering is required for chromatin-based nuclear mechanical response.

Nucleic Acids Res. 2025-8-11

[5]
Herpes simplex virus-1 fluidizes the nucleus enabling condensate formation.

bioRxiv. 2025-6-21

[6]
The mitotic chromosome periphery modulates chromosome mechanics.

Nat Commun. 2025-7-10

[7]
Live-cell magnetic manipulation of recycling endosomes reveals their direct effect on actin protrusions to promote invasive migration.

Sci Adv. 2025-7-4

[8]
Viscoelastic differences between isolated and live MCF7 cancer cell nuclei resolved with AFM microrheology.

J R Soc Interface. 2025-6

[9]
Transcriptional activity generates chromatin motion that drives nuclear blebbing.

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[10]
Intracellular Proteins Targeting with Bi-Functionalized Magnetic Nanoparticles Following their Endosomal Escape.

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