Geometric variations in nucleosomal DNA dictate higher-order chromatin structure and enhancer–promoter communication

Abstract

The dynamic organization of chromatin plays an essential role in the regulation of genetic activity, interconverting between open and compact forms at the global level. The mechanisms underlying these large-scale changes remain a topic of widespread interest. The simulations of nucleosome-decorated DNA reported herein reveal profound effects of the nucleosome itself on overall chromatin properties. Models that capture the long-range communication between proteins on nucleosome-decorated DNA chains incorporate DNA pathways different from those that were previously proposed based on ultracentrifugation and chemical cross-linking data. New quantitative biochemical assays measuring the rates of communication between interacting proteins bound to a promoter and an enhancer at the ends of saturated, precisely positioned, nucleosome-decorated DNA chains reveal a chromatin architecture with a three-nucleosome repeat, a model inconsistent with the two-start configurations deduced from earlier physical studies. Accompanying computations uncover small differences in the twisting of successive base pairs that seemingly give rise to the observed global properties. These data suggest that the novel state of chromatin determined under physiological conditions differs from that deduced under standard physical conditions, likely reflecting the different salt conditions used in the two types of experiments. This novel chromatin state may be important for a number of DNA transactions that occur in the cell nucleus.