Being the basic packaging unit of DNA, the nucleosome core particle (NCP) stabilizes as well as controls DNA accessibility during vital cellular processes. Recently reported structures of the NCP suggest that the histone octamer undergoes conformational changes during the process of DNA translocation around the histone octamer (Bilokapic, Nature Communications, 2018). The mechanism of repositioning of the DNA around the histone octamer has been suggested to be sequence-dependent. Furthermore, the histone tails are suggested here to play a key role in this repositioning. Herein, we demonstrate with long-time all-atomistic molecular dynamics simulations (5 microseconds) that the histone tails do indeed play a critical role in nucleosome repositioning through formation of a loop of nucleosomal DNA around the histone core at high salt concentrations (2 M NaCl). Specifically, we find that the collapse of the H2B tail and subsequent complexation with the minor groove of nucleosomal DNA promotes formation of a ~ 10 bp loop after 2 microseconds. The complexation of the tail increases the local flexibility of the DNA, as characterized by local force constants. Upon collapse of the tail, counterions are released. In addition, using normal mode analysis, we also identify a ‘wave-like motion’ of nucleosomal DNA. Next, we perform umbrella sampling to characterize two possible pathways of the initial stages of unwrapping, using the radius of gyration of the DNA as a reaction coordinate. These results suggest that regulation of the histone tail interactions with nucleosomal DNA may play a critical role in nucleosomal dynamics by acting as a switch to determine the initial pathway of unwrapping.

Molecular mechanism for the role of histone tails in nucleosome repositioning

2019 Spring National Meeting

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