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Cryo-ET Delivers First Detailed 3D Map of Chromatin Condensates

The study links linker-DNA length to nucleosome packing, shaping condensate material properties.

Overview

  • Researchers from UT Southwestern, UC San Diego, the University of Cambridge, and HHMI Janelia used cryo-electron tomography with cryo-focused ion beam milling on flash-frozen samples to reconstruct condensate interiors at high resolution, as reported in Science on Dec. 4, 2025.
  • The reconstructions resolved nucleosome positions within synthetic droplets and, together with light microscopy and coarse-grained simulations, produced a multiscale model that connects molecular arrangements to emergent condensate behavior.
  • Varying the length of linker DNA changed chromatin fiber packing and network connectivity, accounting for differences in phase separation propensity and material properties across chromatin types.
  • Imaging and analyses showed that lab-made chromatin condensates closely mimic the organization of compacted DNA observed in cells.
  • A multi-institution Chromatin Consortium effort, convening at the Marine Biological Laboratory and integrating imaging from HHMI Janelia, is presented as a framework for studying other condensates and probing disease-related condensation.