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

S. Basu, O. Shukron, D. Hall, P. Parutto, A. Ponjavic, D. Shah, W. Boucher, D. Lando, W. Zhang, N. Reynolds, L. H. Sober, A. Jartseva, R. Ragheb, X. Ma, J. Cramard, R. Floyd, J. Balmer, T. A. Drury, A. R. Carr, L. M. NeedhamA. Aubert, G. Communie, K. Gor, M. Steindel, L. Morey, E. Blanco, T. Bartke, L. Di Croce, I. Berger, C. Schaffitzel, S. F. Lee, T. J. Stevens, D. Klenerman*, B. D. Hendrich*, D. Holcman*, E. D. Laue*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1628-1639
Number of pages12
JournalNature Structural and Molecular Biology
Volume30
Issue number11
DOIs
Publication statusPublished - Nov 2023
Externally publishedYes

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