The nucleosome: from structure to function through physics

Abstract

Eukaryotic cells must fit meters of DNA into micron-sized cell nuclei and, at the same time, control and modulate the access to the genetic material. The necessary amount of DNA compaction is achieved via multiple levels of structural organization, the first being the nucleosome-a unique complex of histone proteins with ∼150 base pairs of DNA. Here we use specific examples to demonstrate that many aspects of the structure and function of nucleosomes can be understood using principles of basic physics, physics-based tools and models. For instance, the stability of a single nucleosome and the accessibility to its DNA depend sensitively on the charges in the histone core, which can be changed by post-translational modifications. The positions of nucleosomes along DNA molecules depend on the sequence-dependent shape and elasticity of the DNA double helix that has to be wrapped into the nucleosome complex. Larger-scale structures composed of multiple nucleosomes, that is nucleosome arrays, depend in turn on the interactions between its constituents that result from delicately tuned electrostatics.