Computer Simulation of Chromatin: Interdependency Between Nucleosome Positions and Chromatin Structure

The three-dimensional structure of chromatin is a key factor for controlling DNA accessibility, replication and repair. Despite numerous experimental efforts many details of the spatial organization and structural regulation mechanisms of chromatin remain unclear.Most theoretical models of chromatin proposed in literature imply a periodical positioning and uniform occupancy of the fiber nucleosomes. However, recent studies suggest a dynamic rather than static nucleosome positioning, which is both actively regulated by chromatin-remodeling complexes (CRCs) and passively influenced by thermal fluctuations. These processes have been subject to intensive scientific work, yielding new insights into the function of CRCs and the biophysical properties of the histone-DNA interface. However, nucleosome positions are also influenced by energetic effects imposed by structural constraints inherent in the chromatin fiber, and, vice versa, nucleosome positioning impacts chromatin fiber structure as well.To investigate the effects of nucleosome repositioning, we carried out Monte Carlo simulations with a coarse-grained chromatin model incorporating elastic fiber properties as well as a detailed description of the electrostatic and internucleosomal interactions. We created computational fiber conformations based on experimental results. These fiber conformations were modified by repositioning nucleosomes by a range of base pair steps. After simulation, the chromatin energy landscape and shape were analyzed. We observed a significant energy barrier against nucleosome repositioning which is larger than thermal fluctuations but within the range of ATP-dependent biological processes. Moreover, analysis of fiber shape data revealed an increased kinking susceptibility of the fiber within the region proximate to a repositioned nucleosome. This behavior is accompanied by increased fiber flexibility within the same region.These findings facilitate a deeper understanding of the relation between nucleosome positions and chromatin fiber structure.