Nucleosome Dynamics

Each nucleosome has its own physical properties - not just because of differences in the protein core but especially as a result of the sequence dependent shape and mechanics of the wrapped DNA double helix. We have studied in detail how this affects the dynamic properties of nucleosomes. One example is nucleosome breathing: parts of the wrapped DNA unwrap spontaneously from the protein core. We use our coarse grained nucleosome model to interpret various types of experiments (restriction enzymes, FRET, SAXS) and to highlight the differences between nucleosomes containing different base-pair sequences (Culkin 2017; van Deelen 2020).

Another important question is how to explain the fact that nucleosomes seem to be much more stable against external forces as one would expect based on other experiments (as e.g. the above mentioned ones). This can be understood as a dynamical phenomenon: in order for a nucleosome to unwrap under force, it has to flip by 180 degrees, severely bending its DNA. This protects nucleosomes kinetically against transient external forces. Our computer model (de Bruin 2016) can explain detailed experimental findings based on a combination of micromanipulation and FRET. Using our Mutation Monte Carlo method we can also design special base-pair sequences which lead to nucleosomes which unwrap encountering hardly any barrier, constituting something like "force sensors" (Tompitak 2017).