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

Citació

  • 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

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Descripció

  • Resum

    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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