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

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

Nat. Struct. Mol. Biol. 30, 1628-1639 (2023)
DOI PMC
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords 3d Genome Architecture; Gene-expression; Histone Deacetylase; Hi-c; Chromatin; Cohesin; Transcription; Complex; Component; Binding
ISSN (print) / ISBN 1545-9993
e-ISSN 1545-9985
Journal Nature Structural & Molecular Biology
Quellenangaben Volume: 30, Issue: 11, Pages: 1628-1639 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place New York, NY
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Functional Epigenetics (IFE)
Grants Cambridge Stem Cell Institute
Wellcome Trust/MRC
Isaac Newton Trust
MRC
Wellcome Trust
Medical Research Council
EU FP7 Integrated Project '4DCellFate'
We thank T. Kretschmann for preparing the figures for publication, L. Lavis (Howard Hughes Medical Institute, Janelia Farm) for providing the JF549 dye, J. Wysocka (Stanford) for the Tbx3 constructs used for 2D enhancer tracking, A. Ridde