CG modeling of nucleosome arrays reveals the salt-dependent chromatin fiber conformational variability

Eukaryotic DNA is packaged in the cell nucleus into chromatin, composed of arrays of DNA-histone protein octamer complexes, the nucleosomes. Over the past decade, it has become clear that chromatin structure in vivo is not a hierarchy of well-organized folded nucleosome fibers but displays considerable conformational variability and heterogeneity. In vitro and in vivo studies, as well as computational modeling, have revealed that attractive nucleosome-nucleosome interaction with an essential role of nucleosome stacking defines chromatin compaction. The internal structure of compacted nucleosome arrays is regulated by the flexible and dynamic histone N-terminal tails. Since DNA is a highly negatively charged polyelectrolyte, electrostatic forces make a decisive contribution to chromatin formation and require the histones, particularly histone tails, to carry a significant positive charge. This also results in an essential role of mobile cations of the cytoplasm (K+, Na+, Mg2+) in regulating electrostatic interactions. Building on a previously successfully established bottom-up coarse-grained (CG) nucleosome model, we have developed a CG nucleosome array (chromatin fiber) model with the explicit presence of mobile ions and studied its conformational variability as a function of Na+ and Mg2+ ion concentration. With progressively elevated ion concentrations, we identified four main conformational states of nucleosome arrays characterized as extended, flexible, nucleosome-clutched, and globular fibers.