The intricate pattern of chemical modifications on the DNA and histones, the "histone code", is considered to be a  gene regulation factor. Multivalency is seen by many as an essential instrument to mediate the transmission of the "encoded" information to the transcription machinery via multi- domain effector proteins and chromatin-associated complexes. However, the physical model explaining the critical role of multivalency for the histone code is still largely unknown . Here, we propose a theory that explains the energetic "payout" of multivalency in the formalism of statistical mechanics. The model quantifies the dependence of binding entropy in a multivalent system on the geometry and flexibility of the binding partners. The model explains how the histone-mediated signalling may rely upon weak individual histone-effector affinities while maintaining high probabilities for simultaneous binding of multiple partners and introduces an entropic "lock-and-key" as a critical component of the histone code .
The intricate pattern of chemical modifications on the DNA and histones, the "histone code", is considered to be a key gene regulation factor. Multivalency is seen by many as an essential instrument to mediate the transmission of the "encoded" information to the transcription machinery via multi- domain effector proteins and chromatin-associated complexes. However, the physical model explaining the critical role of multivalency for the histone code is still lacking . Here, we propose a theory that explains the energetic "payout" of multivalency in the formalism of statistical mechanics. The model quantifies the dependence of binding entropy in a multivalent system on the geometry and flexibility of the binding partners. An all-atom molecular dynamics study of a relevant biological system involving the multivalent chromatin effector UHRF1 and its target histone H3 demonstrate that this interaction conforms to the conditions for an optimal free-energy payout, as predicted by the model .
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key
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largely unknown
lacking
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The model explains how the histone-mediated signalling may rely upon weak individual histone-effector affinities while maintaining high probabilities for simultaneous binding of multiple partners and introduces an entropic "lock-and-key" as a critical component of the histone code
An all-atom molecular dynamics study of a relevant biological system involving the multivalent chromatin effector UHRF1 and its target histone H3 demonstrate that this interaction conforms to the conditions for an optimal free-energy payout, as predicted by the model