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

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  • dc.contributor.author Basu, Srinjan
  • dc.contributor.author Blanco, Enrique
  • dc.contributor.author Laue, Ernest D.
  • dc.date.accessioned 2024-01-23T07:24:19Z
  • dc.date.available 2024-01-23T07:24:19Z
  • dc.date.issued 2023
  • dc.description.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.
  • dc.description.sponsorship We thank the EU FP7 Integrated Project ‘4DCellFate’ (277899 E.D.L., B.D.H., I.B., C.S. and L.D.C.), the Medical Research Council (MR/P019471/1 E.D.L.) and the Wellcome Trust (206291/Z/17/Z E.D.L.) for program funding. We also thank the MRC (MR/R009759/1 B.D.H., and MR/M010082/1 E.D.L.), the Wellcome Trust (106115/Z/14/Z I.B. and 210701/Z/18/Z C.S.) and the Isaac Newton Trust (17.24(aa) B.D.H.) for project grant funding, and we thank the Wellcome Trust/MRC for core funding (203151/Z/16/Z) to the Cambridge Stem Cell Institute (including a starter grant to S.B.).
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Basu S, Shukron O, Hall D, Parutto P, Ponjavic A, Shah D, et al. Live-cell three-dimensional single-molecule tracking reveals modulation of enhancer dynamics by NuRD. Nat Struct Mol Biol. 2023 Nov;30(11):1628-39. DOI: 10.1038/s41594-023-01095-4
  • dc.identifier.doi http://dx.doi.org/10.1038/s41594-023-01095-4
  • dc.identifier.issn 1545-9993
  • dc.identifier.uri http://hdl.handle.net/10230/58804
  • dc.language.iso eng
  • dc.publisher Nature Research
  • dc.relation.ispartof Nat Struct Mol Biol. 2023 Nov;30(11):1628-39
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/277899
  • dc.rights © The Author(s) 2023, corrected publication 2023. Open Access 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/.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword Cellular imaging
  • dc.subject.keyword Chromatin remodelling
  • dc.subject.keyword Chromatin structure
  • dc.title Live-cell three-dimensional single-molecule tracking reveals modulation of enhancer dynamics by NuRD
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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