DNA spontaneously wrapping around a histone core prefers negative supercoiling: A Brownian dynamics study

Abstract In eukaryotes, DNA achieves a highly compact structure primarily due to its winding around the histone cores. The nature wrapping of DNA around histone core form a 1.7 left-handed superhelical turns, contributing to negative supercoiling in chromatin. On the contrary, negative supercoils generated behind the polymerase during transcription may play a role in triggering nucleosome reassembly. To elucidate how supercoils influence the dynamics of wrapping of DNA around the histone cores, we developed a novel model to simulate the intricate interplay between DNA and histone. Our simulations revealed that both positively and negatively supercoiled DNAs are capable of wrapping around histone cores to adopt the nucleosome conformation. Most of all, our findings confirmed a preference for negative supercoiled DNA during nucleosome wrapping, and revealed that the both of the negative writhe and twist are comparatively beneficial to the formation of the DNA wrapping around histone. This advancement in the understanding of spontaneously nucleosome formation may provide insights into the intricate dynamics of chromatin assembly and its diverse functions. Our model thus can be further utilized to simulate the formations of multi-nucleosomes during re-assembling of the chromatin fiber, which will significantly enhance the understanding of the fundamental mechanisms governing the structure and function of chromatin. Author summary The compacted organization of DNA within chromatin is primarily attributed to its intricate winding around histone cores. This winding process involves 1.7 left-handed superhelical turns around the histone core, contributing to the negative supercoiling within chromatin fibers. To gain deeper insights into how DNA supercoiling impacts the dynamics of DNA wrapping around histone cores, we devised a novel computational model that simulates the intricate interplay between DNA and histone cores. Additionally, our simulations revealed that both of the positively and negatively supercoiled DNA can spontaneously adopt the nucleosome conformation upon wrapping around the histone core, and demonstrated a preferential tendency for negative supercoiling during nucleosome wrapping. Finally, we examined that both the negative writhe and twist components are comparatively advantageous for the formation of the nucleosome. The studies shed light on the intricate dynamics underlying chromatin assembly and its functional implications.