ArticleProceedings of the National Academy of Sciences of the United States of America2025
Quantitative spatial analysis of chromatin biomolecular condensates using cryoelectron tomography.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed.
- AI-assisted Cryo-ET workflow for 3D visualization of chromatin during cellular differentiation.Biochemistry and biophysics reports · 2026Article
- Progress toward linking single-molecule behavior and condensate material properties.Current opinion in structural biology · 2026Review
- Molecular architecture of heterochromatin at the nuclear periphery of primary human cells.Nature communications · 2026Article
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- Article
- Nucleosome condensate and linker DNA alter chromatin folding pathways and rates.Biophysical journal · 2026Article
- ExoSloNano: multimodal nanogold labels for identification of macromolecules in live cells and cryo-electron tomograms.Nature methods · 2026Article
- Multiscale structure of chromatin condensates explains phase separation and material properties.Science (New York, N.Y.) · 2025Article
- An electrostatic repulsion model of centromere organisation.bioRxiv : the preprint server for biology · 2025Article
- Biomolecular condensates in plant immunity.Cell host & microbe · 2025Review
- In-cell chromatin structure by Cryo-FIB and Cryo-ET.Current opinion in structural biology · 2025Review
- Nanometer condensate organization in live cells derived from partitioning measurements.bioRxiv : the preprint server for biology · 2025Article
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Abstract
Phase separation is an important mechanism to generate certain biomolecular condensates and organize the cell interior. Condensate formation and function remain incompletely understood due to difficulties in visualizing the condensate interior at high resolution. Here, we analyzed the structure of biochemically reconstituted chromatin condensates through cryoelectron tomography. We found that traditional blotting methods of sample preparation were inadequate, and high-pressure freezing plus focused ion beam milling was essential to maintain condensate integrity. To identify densely packed molecules within the condensate, we integrated deep learning-based segmentation with context-aware template matching. Our approaches were developed on chromatin condensates and were also effective on condensed regions of in situ native chromatin. Using these methods, we determined the average structure of nucleosomes to 6.1 and 12 Å resolution in reconstituted and native systems, respectively, found that nucleosomes form heterogeneous interaction networks in both cases, and gained insight into the molecular origins of surface tension in chromatin condensates. Our methods should be applicable to biomolecular condensates containing large and distinctive components in both biochemical reconstitutions and certain cellular systems.
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