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)
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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Article: Journal article
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3d Genome Architecture; Gene-expression; Histone Deacetylase; Hi-c; Chromatin; Cohesin; Transcription; Complex; Component; Binding
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1545-9993
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1545-9985
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Volume: 30,
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Pages: 1628-1639
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Nature Publishing Group
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New York, NY
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Cambridge Stem Cell Institute
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Isaac Newton Trust
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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
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