Live-cell three-dimensional single-molecule tracking reveals modulation of enhancer dynamics by NuRD

Abstract

To understand how the nucleosome remodeling and deacetylase (NuRD) complex regulates enhancers and enhancer–promoter interactions, we have developed an approach to segment and extract key biophysical parameters from live-cell three-dimensional single-molecule trajectories. Unexpectedly, this has revealed that NuRD binds to chromatin for minutes, decompacts chromatin structure and increases enhancer dynamics. We also uncovered a rare fast-diffusing state of enhancers and found that NuRD restricts the time spent in this state. Hi-C and Cut&Run experiments revealed that NuRD modulates enhancer–promoter interactions in active chromatin, allowing them to contact each other over longer distances. Furthermore, NuRD leads to a marked redistribution of CTCF and, in particular, cohesin. We propose that NuRD promotes a decondensed chromatin environment, where enhancers and promoters can contact each other over longer distances, and where the resetting of enhancer–promoter interactions brought about by the fast decondensed chromatin motions is reduced, leading to more stable, long-lived enhancer–promoter relationships.

Metadata

Item Type:	Article
Authors/Creators:	Basu, S. https://orcid.org/0000-0002-1080-979X Shukron, O. Hall, D. https://orcid.org/0000-0001-5284-609X Parutto, P. https://orcid.org/0000-0002-9866-407X Ponjavic, A. https://orcid.org/0000-0002-7561-1127 Shah, D. Boucher, W. Lando, D. https://orcid.org/0000-0001-5783-8769 Zhang, W. Reynolds, N. Sober, L.H. Jartseva, A. Ragheb, R. https://orcid.org/0000-0001-5892-1767 Ma, X. Cramard, J. https://orcid.org/0000-0003-1041-8913 Floyd, R. Balmer, J. Drury, T.A. Carr, A.R. Needham, L.-M. https://orcid.org/0000-0002-8139-5862 Aubert, A. Communie, G. Gor, K. Steindel, M. Morey, L. https://orcid.org/0000-0001-9851-4066 Blanco, E. https://orcid.org/0000-0001-6261-7370 Bartke, T. https://orcid.org/0000-0002-6584-2140 Di Croce, L. https://orcid.org/0000-0003-3488-6228 Berger, I. https://orcid.org/0000-0001-7518-9045 Schaffitzel, C. https://orcid.org/0000-0002-1516-9760 Lee, S.F. https://orcid.org/0000-0003-4492-5139 Stevens, T.J. https://orcid.org/0000-0001-6475-2074 Klenerman, D. https://orcid.org/0000-0001-7116-6954 Hendrich, B.D. https://orcid.org/0000-0002-0231-3073 Holcman, D. https://orcid.org/0000-0001-9854-5014 Laue, E.D. https://orcid.org/0000-0002-7476-4148
Copyright, Publisher and Additional Information:	© The Author(s) 2023. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Keywords:	Chromatin; Nucleosomes; Enhancer Elements, Genetic; Promoter Regions, Genetic; Mi-2 Nucleosome Remodeling and Deacetylase Complex
Dates:	Published: November 2023 Published (online): 28 September 2023 Accepted: 14 August 2023
Institution:	The University of Leeds
Academic Units:	The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Physics and Astronomy (Leeds) > Molecular & Nanoscale Physics
Depositing User:	Symplectic Publications
Date Deposited:	13 Dec 2023 11:00
Last Modified:	13 Dec 2023 11:00
Status:	Published
Publisher:	Springer
Identification Number:	10.1038/s41594-023-01095-4
Related URLs:	PubMed URL
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:206565

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Live-cell three-dimensional single-molecule tracking reveals modulation of enhancer dynamics by NuRD

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