The role of polarization interactions in the wrapping/unwrapping of nucleosomal DNA around the histone octamer: Implications to gene regulation

The inclusion of polarization interactions in nucleic acids and proteins have been recognized as a major improvement both in our understanding of these systems and in the accuracy of current calculations and simulations. Recently, we have investigated the role of these interactions in DNA A-tracts bending using a Monte Carlo simulation approach developed by Jarque and Buckingham, which allows the explicit calculation of the polarization energy at the microscopic level as a function of the interionic distance for two charges embedded in a polarizable medium. Here, we investigate the role of polarization interactions in providing a framework for understanding the wrapping/unwrapping of nucleosomal DNA. The effective electrostatic potential energy is found to decrease as the nucleosomal DNA minor groove width is decreased. This results in bending of DNA which gives rise to its folding, with narrow minor grooves facing in toward the octamer. Changes in the structure of the nucleosome, through its intrinsic dynamics, ATP-dependent remodeling factors or covalent modifications of the histone tails, and/or in the strength of hydration would exert profound effects on the strength of the polarization interactions and thereby could modulate the folding of DNA and the transcription process. These considerations have led us to suggest a potential epigenetic mechanism according to which the grip of DNA on the histone core could be controlled by the width of the minor groove in conjunction with the local compactness of the nucleosome and the strength of hydration.