In silico evidence for sequence-dependent nucleosome sliding

In recent work by Lequieu et al., researchers from the de Pablo group have made important progress in understanding the molecular processes that control the dynamics of the smallest building-block of chromatin, a DNA-protein complex called the nucleosome. Their findings, published this week in Proceedings of the National Academy of Sciences, show how the nucleosome dynamics are encoded in the DNA sequence, and demonstrate that nucleosomes with different DNA sequences reposition through dramatically different mechanisms. This surprising result helps explain how the complex three-dimensional structure of chromatin is related the individual nucleic acids of which it is composed.

Lequieu et al. also demonstrate that, under some circumstances, these sequence-directed dynamics can be overwritten. In particular, they show that proteins that apply small amounts of torque to the DNA can effectively erase the role of DNA sequence in nucleosome dynamics. The picture that emerges from their study is one in which biology relies on a subtle balance between different molecular factors to perform it genetic functions; by relying on simple molecular cues, a cell can dramatically alter the structure and dynamics of its chromatin. More broadly, these findings have significant implications for understanding chromatin, and could play a role in understanding the wide range of diseases, including cancer, that are associated with errors in chromatin compaction.

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