Modeling the regulation of chromatin dynamics by redox modifications

Zineb Elftmaoui1, Emmanuelle Bignon1
1 Université de Lorraine and CNRS, UMR 7019 LPCT, F-54000 Nancy, France

Understanding the molecular mechanisms underlying the nucleosome dynamics impact on chromatin structure regulation and genome functioning is a timely area of research. It is known that histone post-translational modifications play an important role in the regulation of the nucleosome plasticity, hence the chromatin organization. The molecular mechanisms behind histone oxidation and their effect on spontaneous nucleosomal DNA breathing, unwrapping, twisting, and sliding is, however, poorly understood. Molecular modeling and simulations are a method of choice to investigate such key-aspects, at the atomic level. We investigated the effect of one of these oxidative modifications, the S-gluathionylation of the histone 3, onto the dynamic behavior of the nucleosome structure. This modifications is known to happen in vivo, has been linked to the opening of the chromatin, and has been shown to be positively correlated to acetylation levels (an other type of post-translational modification).

In this talk, a study showing how the S-glutathionylation impacts the nucleosome dynamics will be presented in a first section. A second section will be dedicated to presenting preliminary results on the binding of the SIRT6 de-acetylase protein onto the nucleosome, which regulates the levels of lysine acetylation of histones, also known to be correlated to levels of S-glutathionylation.