Ion counting demonstrates a high electrostatic potential of the nucleosome

Abstract

AbstractThe fundamental unit of chromatin is the nucleosome, which comprises of DNA wrapped around a histone protein octamer. The association of positively charged histone proteins with negatively charged DNA is intuitively thought to attenuate the electrostatic repulsion of DNA, resulting in a weakly charged nucleosome complex. In contrast, theoretical and computational studies suggest that the nucleosome retains a strong, negative electrostatic field. Despite their fundamental implications for chromatin organization and function, these opposing models have not been experimentally tested. Herein, we directly measure nucleosome electrostatics and find that while nucleosome formation reduces the complex charge by half, the nucleosome nevertheless maintains a strong negative electrostatic field. Further, our results show that the wrapping of DNA around a histone octamer increases the propensity of the DNA to make interactions with multivalent cations like Mg2+. These findings indicate that presentation of DNA on a nucleosome may more strongly attract positively-charged DNA binding proteins. Our studies highlight the importance of considering the polyelectrolyte nature of the nucleosome and its impact on processes ranging from factor binding to DNA compaction.