Structural effects of H4K16 acylations characterized by mesoscale simulation

H4K16 acylations have been implicated in significant biological effects such as the formation of euchromatic nuclear sub-compartments and medical conditions such as Propionic Acidemia, but the molecular mechanisms underlying these effects are just beginning to be understood. Recent experimental analysis of key nucleosomal physics through single-molecule force spectrometry and structural probing has allowed the development and validation of fast mesoscale polymer models for chromatin structure which directly incorporate these acylations, providing a potential avenue for understanding their impact on local chromatin structure. In this work, we perform mesoscale simulations of 12-nucleosome chromatin fibers with three different H4K16 acylations, deriving key model parameters directly from experiments performed in concert, analyze the impact of these acylations on fiber structure, and compare our predictions to the available body of experimental data. Ultimately, we find that H4K16Ac and H4K16Bu significantly disrupt internucleosome interactions, resulting in significantly less compact fibers with dramatically increased accessible DNA surface area. Unexpectedly, we find that key properties of H4K16Pr change the local folding geometry of chromatin fibers, without causing significant decompaction. Our results provide unique insight into the range of possible structural impacts of H4K16 acylations, and may provide the scientific community with a starting point for understanding the novel biological effects of these post-translational modifications.