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bioRxiv · 10.64898/2026.01.06.698048

Valency-driven division of labor balances chromatin compaction and structural plasticity

Tang, J.·Chu, X.
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Abstract

Chromatin folding is regulated by multivalent protein complexes and condensates, yet how the multivalent binding quantitatively controls chromatin compaction, domain organization, and cell-to-cell heterogeneity remains unresolved. Here we develop the Chromatin-associated Protein Complex Maximum Entropy Model (CPC-MEM), a data-driven, physics-based polymer framework in which Hi-C contacts are realized through an explicit, finite pool of diffusing chromatin-associated protein complexes (CPCs) with prescribed CPC-chromatin interaction valency. When fitted to Hi-C, CPC-MEM generates chromatin structural ensembles that simultaneously reproduce population-averaged contact maps and single-cell super-resolution distance statistics. We uncover a clear division of labor across valency: low-valency CPCs act as abundant linkers that compact chromatin, homogenize folding, and refine local structure, whereas high-valency CPCs form sparse co-bridging hubs that nucleate chromatin domains and increase conformational heterogeneity. Mixtures of valencies naturally produce a "hub-and-matrix" chromatin architecture that optimally balances compaction with structural plasticity. Our study provides a quantitative mechanism by which locus-specific chromatin interaction preferences, together with the valency and abundance of CPCs and condensates in the nucleus, jointly shape functional 3D genome organization.

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Tang, J., Chu, X.. 2026-01-07. Valency-driven division of labor balances chromatin compaction and structural plasticity. https://doi.org/10.64898/2026.01.06.698048

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