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Tail bridging vs. patchiness: models for the interaction of nucleosomes


Mühlbacher,  Frank
MPI for Polymer Research, Max Planck Society;

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Mühlbacher, F. (2004). Tail bridging vs. patchiness: models for the interaction of nucleosomes. PhD Thesis, Johannes Gutenberg-Universität, Mainz.

Abstract: The subject of this thesis are the interactions between nucleosome core particles (NCPs). NCPs are the primary storage units of DNA in eucaryotic cells. Each NCP consists of a core of eight histone proteins and a strand of DNA, which is wrapped around about two times. Each histone protein has a terminal tail passing over and between the superhelix of the wrapped DNA. Special emphasis was placed on the role of the histone tails, since experimental findings suggest that the tails have a great influence on the mutual attraction of the NCPs. In those experiments Mangenot et al. observe a dramatic change in the configuration of the tails, which is accompanied by evidence of mutual attraction between NCPs, when a certain salt concentration is reached. Existing models used in the theoretical approaches and in simulations focus on the description of the histone core and the wrapped DNA, but neglect the histone tails. We introduce the multi chain complex as a new simulation model. Here the histone core and the wrapping DNA are modelled via a charged sphere, while the histone tails are represented by oppositely charged chains grafted on the sphere surface. We start by investigating the parameter space describing a single NCP. The Debye-H\"uckel potential is used to model the electrostatic interactions and to determine the effective charge of the NCP core. This value is subsequently used for a study of the pair-interaction of two NCPs via an extensive Molecular Dynamics study. The monomer distribution of the full chain model is investigated. The existence of tail bridges between the cores is demonstrated. Finally, by discriminating between bridging and non-bridging configurations, we can show that the effect of tail bridging between the spheres does indeed account for the observed attraction. The full chain model can serve as a model to study the acetylation of the histone tails of the nucleosome. The reduction of the charge fraction of the tails, that corresponds to the process of acetylation, leads to a reduction or even the disappearance of the attraction. A recent MC study links this effect to the unfolding of the chromatin fiber in the case of acetylated histone tails. In this case the acetylation of the histone tails leads to the formation of heterochromatin, and one could understand how larger regions of the genetic information could be inactivated through this mechanism.