Projects per year
Abstract
The compaction of chromatin is a prevalent paradigm in gene repression. Chromatin compaction is commonly thought to repress transcription by restricting chromatin accessibility. However, the spatial organization and dynamics of chromatin compacted by gene-repressing factors are unknown. Here, using cryo-electron tomography, we solved the three-dimensional structure of chromatin condensed by the polycomb repressive complex 1 (PRC1) in a complex with CBX8. PRC1-condensed chromatin is porous and stabilized through multivalent dynamic interactions of PRC1 with chromatin. Mechanistically, positively charged residues on the internally disordered regions of CBX8 mask negative charges on the DNA to stabilize the condensed state of chromatin. Within condensates, PRC1 remains dynamic while maintaining a static chromatin structure. In differentiated mouse embryonic stem cells, CBX8-bound chromatin remains accessible. These findings challenge the idea of rigidly compacted polycomb domains and instead provide a mechanistic framework for dynamic and accessible PRC1–chromatin condensates.
Original language | English |
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Article number | eaba8811 |
Number of pages | 32 |
Journal | Nature Structural & Molecular Biology |
Volume | 32 |
Issue number | 3 |
DOIs | |
Publication status | Published - 2025 |
Projects
- 4 Finished
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Rewriting the dogma of chromatin compaction: a new pathway for polycomb-mediated gene repression in development and disease
Davidovich, C. (Primary Chief Investigator (PCI)), Uckelmann, M. (Chief Investigator (CI)), Zhang, Q. (Associate Investigator (AI)), de Marco, A. (Associate Investigator (AI)) & Das, P. (Associate Investigator (AI))
1/01/22 → 31/12/24
Project: Research
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Polycomb Group Proteins - Shaping Chromatin Architecture to Silence Genes
Uckelmann, M. (Primary Chief Investigator (PCI))
ARC - Australian Research Council
14/01/21 → 31/12/24
Project: Research
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RNA-mediated regulation of the histone methyltransferase PRC2: a new link to disease-associated and causing mutations
Davidovich, C. (Primary Chief Investigator (PCI))
1/01/19 → 31/12/21
Project: Research
Equipment
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High-performance Computing (M3/MASSIVE)
Powell, D. (Manager) & Tan, G. (Manager)
Office of the Vice-Provost (Research and Research Infrastructure)Facility/equipment: Facility
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Monash Proteomics & Metabolomics Platform (MPMP)
Schittenhelm, R. (Other) & Steer, D. (Manager)
Faculty of Medicine Nursing and Health Sciences Research PlatformsFacility/equipment: Facility
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Ramaciotti Centre for Cryo-Electron Microscopy (CryoEM)
Ramm, G. (Manager), Crawford, S. A. (Operator), Venugopal, H. (Operator), Clark, J. M. (Operator) & Gervinskas, G. (Operator)
Faculty of Medicine Nursing and Health Sciences Research PlatformsFacility/equipment: Facility