Dynamic PRC1-CBX8 stabilizes a porous structure of chromatin condensates
Date
2025
Authors
Uckelmann, M.
Levina, V.
Taveneau, C.
Ng, X.H.
Pandey, V.
Martinez, J.
Mendiratta, S.
Houx, J.
Boudes, M.
Venugopal, H.
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Journal article
Citation
Nature Structural & Molecular Biology, 2025; 32(3):520-530
Statement of Responsibility
Michael Uckelmann, Vita Levina, Cyntia Taveneau, Xiao Han Ng, Varun Pandey, Jasmine Martinez, Shweta Mendiratta, Justin Houx, Marion Boudes, Hari Venugopal, Sylvain Trépout, Alex J. Fulcher, Qi Zhang, Sarena Flanigan, Minrui Li, Emma Sierecki, Yann Gambin, Partha Pratim Das, Oliver Bell, Alex de Marco, Chen Davidovich
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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.
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© The Author(s) 2025. This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.