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

Autor: Keizer VIP; 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.; Institut Curie, PSL Research University, CNRS UMR144, Laboratoire Biologie Cellulaire et Cancer, 75005 Paris, France., Grosse-Holz S; 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.; Department of Physics and Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., Woringer M; 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., Zambon L; 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.; Institut Curie, PSL Research University, CNRS UMR144, Laboratoire Biologie Cellulaire et Cancer, 75005 Paris, France., Aizel K; Institut Curie, PSL Research University, Sorbonne Université, CNRS UMR168, Laboratoire Physico Chimie Curie, 75005 Paris, France., Bongaerts M; Institut Curie, PSL Research University, Sorbonne Université, CNRS UMR168, Laboratoire Physico Chimie Curie, 75005 Paris, France., Delille F; ESPCI Paris, PSL Research University, Sorbonne Université, CNRS UMR8213, Laboratoire de Physique et d'Étude des Matériaux, 75005 Paris, France., Kolar-Znika L; 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., Scolari VF; 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., Hoffmann S; Institut Curie, PSL Research University, CNRS UMR144, Laboratoire Biologie Cellulaire et Cancer, 75005 Paris, France., Banigan EJ; Department of Physics and Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., Mirny LA; Institut Curie, PSL Research University, Sorbonne Université, CNRS UMR3664, Laboratoire Dynamique du Noyau, 75005 Paris, France.; Department of Physics and Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., Dahan M; Institut Curie, PSL Research University, Sorbonne Université, CNRS UMR168, Laboratoire Physico Chimie Curie, 75005 Paris, France., Fachinetti D; Institut Curie, PSL Research University, CNRS UMR144, Laboratoire Biologie Cellulaire et Cancer, 75005 Paris, France., Coulon A; 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.
Jazyk: angličtina
Zdroj: Science (New York, N.Y.) [Science] 2022 Jul 29; Vol. 377 (6605), pp. 489-495. Date of Electronic Publication: 2022 Jul 28.
DOI: 10.1126/science.abi9810
Abstrakt: 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.
Databáze: MEDLINE
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