Multiscale structure of chromatin condensates explains phase separation and material properties
The structure and interaction networks of molecules within biomolecular condensates are poorly understood. Using cryo-electron tomography and molecular dynamics simulations, we elucidated the structure of phase-separated chromatin condensates across scales, from individual amino acids to network architecture. We found that internucleosomal DNA linker length controls nucleosome arrangement and histone tail interactions, shaping the structure of individual chromatin molecules within and outside condensates. This structural modulation determines the balance between intra- and intermolecular interactions, which governs the molecular network, thermodynamic stability, and material properties of chromatin condensates. Mammalian nuclei contain dense clusters of nucleosomes whose nonrandom organization is mirrored by the reconstituted condensates. Our work explains how the structure of individual chromatin molecules determines physical properties of chromatin condensates and cellular chromatin organization.
Authors
- Nirnay Samanta (ORCID: https://orcid.org/0000-0002-5746-6907)
- Joshua Hutchings (ORCID: https://orcid.org/0000-0001-6841-8583)
- Michael K. Rosen (ORCID: https://orcid.org/0000-0002-0775-7917)
- Andrea Soranno (ORCID: https://orcid.org/0000-0001-8394-7993)
- Huabin Zhou (ORCID: https://orcid.org/0000-0002-7788-0806)
- Jorge R. Espinosa (ORCID: https://orcid.org/0000-0001-9530-2658)
- Ramya Billur (ORCID: https://orcid.org/0000-0002-8677-0801)
- Lynda K. Doolittle
- Bryan A. Gibson (ORCID: https://orcid.org/0000-0002-9657-7466)
- Margot Riggi
- Maria Julia Maristany (ORCID: https://orcid.org/0009-0009-8875-9225)
- Zhiheng Yu (ORCID: https://orcid.org/0000-0002-7114-2570)
- Run-Wen Yao (ORCID: https://orcid.org/0000-0002-6183-0273)
- Momoko Shiozaki (ORCID: https://orcid.org/0000-0002-5640-8959)
- Rosana Collepardo‐Guevara (ORCID: https://orcid.org/0000-0003-1781-7351)
- Elizabeth Villa (ORCID: https://orcid.org/0000-0003-4677-9809)
- Xiaowei Zhao (ORCID: https://orcid.org/0000-0002-9868-5102)
- Jan Huertas (ORCID: https://orcid.org/0000-0003-2607-5214)
- Kieran Russell
- June Ho Hwang (ORCID: https://orcid.org/0000-0001-6199-1467)
Institutions
- St. Jude Children's Research Hospital (US)
- Marine Biological Laboratory (US)
- Howard Hughes Medical Institute (US)
- Janelia Research Campus (US)
- Washington University in St. Louis (US)
- University of Cambridge (GB)
- University of California San Diego (US)
- Max Planck Institute of Biochemistry (DE)
- The University of Texas Southwestern Medical Center (US)
Publication Details
- Journal
- Science
- Published
- 2025-12-04
- DOI
- https://doi.org/10.1126/science.adv6588
- Citations
- 10
- Primary Topic
- Genomics and Chromatin Dynamics
- Type
- article
- Field-Weighted Citation Impact
- 8.06