Flexibility Of Nucleosomes On Topologically Constrained DNA

The nucleosome plays an ever increasing role in our comprehension of the regulation of gene activity. Here we review our results on nucleosome conformational flexibility, its molecular mechanism and its functional relevance. Our initial approach combined both empirical measurement and theoretical simulation of the topological properties of single particles reconstituted on DNA minicircles. Two types of particles were studied in addition to the conventional nucleosome: a subnucleosome consisting of DNA wrapped around the (H3-H4)2 histone tetramer, now known as a tetrasome, and the linker histone H5/H1-bearing nucleosome, or chromatosome. All particles were found to thermally fluctuate between two to three conformational states, which differed by their topological and mechanical characteristics. These findings were confirmed for the nucleosome and the tetrasome by the use of magnetic tweezers to apply torsions to single arrays of these particles reconstituted on linear DNA. These latter experiments further revealed a new structural form of the nucleosome, the reversome, in which DNA is wrapped in a right-handed superhelical path around a distorted octamer. This work suggests that the single most important role of chromatin may be to considerably increase overall DNA flexibility, which might indeed be a requirement of genome function.