DNA nanomechanics in the nucleosome

The sequence-dependent mechanics of DNA-histone binding are essential for nucleosome positioning and mobility. Here we reanalyze nucleosome crystal structures in terms of the well-characterized base-pair scale DNA elasticity, extracting the forces and torques acting on all bound DNA base pairs. We find that the strongest forces follow a characteristic repeating pattern that recovers the 12 known DNA backbone-histone contact sites. DNA twist defects and histone point mutations modify this pattern in interpretable ways. Additional, irregular forces between contact sites reveal histone tail-DNA interactions, whereas requiring the absence of external forces leads to a structural refinement of linker DNA. Based on these observations, we propose a simple, structure-based mechanical model of the nucleosome that is able to explain the placement of DNA twist defects in 146 base-pair nucleosomes and allows an estimate of the elastic energy spectrum of nucleosome twist defect states.