Co-condensation and multivalency enable acetylation-sensitive, concentration-robust assembly of BRD4 condensates
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| Format: | Preprint |
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2026
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| _version_ | 1866914623159009280 |
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| author | Polyachenko, Yury Watanabe, Hans-Frederick Korolev, Alexei Jacobs, William M. |
| author_facet | Polyachenko, Yury Watanabe, Hans-Frederick Korolev, Alexei Jacobs, William M. |
| contents | Biomolecular condensates must assemble at specific locations and times inside living cells to perform their biological functions. However, it remains unclear how condensate formation achieves high spatiotemporal precision, responding sensitively to local chemical modifications while remaining robust to fluctuations in protein concentration. Here we study chromatin-associated BRD4 condensates to identify a physical mechanism that enables this combination of sensitivity and robustness. Using an ultra-coarse-grained molecular-dynamics model, we show that co-condensation of BRD4 with chromatin enables rapid assembly below the bulk coexistence concentration, thereby suppressing off-chromatin condensation and enhancing spatial selectivity. Multivalent binding between BRD4 and acetylated histone tails sharpens the dependence of co-condensation on acetylation density through combinatorial effects, increasing contrast between highly acetylated regions and weakly acetylated background chromatin. This mechanism explains how co-condensation and multivalent binding jointly enable sensitive yet robust spatiotemporal targeting by chromatin-associated condensates. |
| format | Preprint |
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arxiv_https___arxiv_org_abs_2606_02275 |
| institution | arXiv |
| publishDate | 2026 |
| record_format | arxiv |
| spellingShingle | Co-condensation and multivalency enable acetylation-sensitive, concentration-robust assembly of BRD4 condensates Polyachenko, Yury Watanabe, Hans-Frederick Korolev, Alexei Jacobs, William M. Biological Physics Soft Condensed Matter Biomolecular condensates must assemble at specific locations and times inside living cells to perform their biological functions. However, it remains unclear how condensate formation achieves high spatiotemporal precision, responding sensitively to local chemical modifications while remaining robust to fluctuations in protein concentration. Here we study chromatin-associated BRD4 condensates to identify a physical mechanism that enables this combination of sensitivity and robustness. Using an ultra-coarse-grained molecular-dynamics model, we show that co-condensation of BRD4 with chromatin enables rapid assembly below the bulk coexistence concentration, thereby suppressing off-chromatin condensation and enhancing spatial selectivity. Multivalent binding between BRD4 and acetylated histone tails sharpens the dependence of co-condensation on acetylation density through combinatorial effects, increasing contrast between highly acetylated regions and weakly acetylated background chromatin. This mechanism explains how co-condensation and multivalent binding jointly enable sensitive yet robust spatiotemporal targeting by chromatin-associated condensates. |
| title | Co-condensation and multivalency enable acetylation-sensitive, concentration-robust assembly of BRD4 condensates |
| topic | Biological Physics Soft Condensed Matter |
| url | https://arxiv.org/abs/2606.02275 |