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This study developed a new computational method to analyze 3D single-molecule trajectories in mouse embryonic stem cells, revealing that the NuRD complex binds chromatin for extended periods, decompacts chromatin, and increases the mobility of enhancers while also modulating their interactions with promoters over longer distances.
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The researchers developed a computational approach to segment 3D single-molecule trajectories and extract biophysical parameters from live mouse embryonic stem cells. They compared wild-type cells with Mbd3-knockout cells (lacking functional NuRD complex). Using 20 ms and 500 ms exposure imaging, they tracked chromatin-bound NuRD molecules and labeled enhancers. The key results show that intact NuRD complex binds chromatin for minutes, increases chromatin decondensation and enhancer dynamics, but restricts the time enhancers spend in a fast, decondensed state. Hi-C and CUT&RUN experiments demonstrated that NuRD modulates enhancer-promoter interactions in active chromatin, allowing contacts over longer distances, and causes a redistribution of CTCF and cohesin. The implications suggest NuRD promotes a chromatin environment that facilitates stable, long-range regulatory interactions.