Monday, June 17, 2013

1306.3421 (Bradley M. Dickson et al.)

Statistical mechanics of the histone code    [PDF]

Bradley M. Dickson, Dmitri B. Kireev
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.
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