Multiscale modeling of chromatin condensates

Recent experiments suggest that phase separation plays a role in the organization of chromatin yet the underlying molecular mechanisms remain unclear. Our work presents a molecular view of chromatin condensates using a multiscale model of chromatin. This multiscale model is efficient enough to access the large length scales of phase separation yet retains chemical details such as post-translational modifications. Our model reproduces recent experiments with phase-separated chromatin fibers and provides molecular information of chromatin condensates at nucleosome resolution. With this information we quantified the effects of histone acetylation on condensate stability and characterized the condensate's chromatin fiber structure. Our results demonstrate that short chromatin fibers form liquid-like condensates. Our results also suggest that chromatin fibers are dynamic and irregularly folded within condensed chromatin and do not contain signatures of a 30-nm chromatin fiber. Lastly we show that chromatin condensates can be disrupted by weakening specific nucleosome-nucleosome orientations and how certain histone-modifications can drive the reorganization of chromatin.