Identification of Potential SOX2 Binding Sites to Nucleosomes via Molecular Modeling

The pioneer SOX2 transcription factor plays an important role in the regulation of gene expression by binding to condensed chromatin and inducing its decondensation. Experimental data on the preferred positions of SOX2 binding to DNA in the context of the nucleosome are contradictory: in some studies, binding to the inner segments of nucleosomal DNA is preferred, in others it binds to the edge segments. In the framework of this work, all possible variants of SOX2 binding to nucleosomal DNA at different distances from the nucleosome center (determined by the superhelix position parameter, SHL) and different orientations of the binding site relative to the nucleosome center (determined by the SHL sign) were analyzed by molecular modeling. It was shown that on an intact nucleosome binding is possible at positions SHL +2, SHL ±4, and SHL ±5, but if we assume a shift of nucleosomal DNA by one pair of nucleotides, binding becomes possible at positions corresponding to all integer values of the SHL. This observation helps to explain some of the contradictions between the experimental data.