  Fluorescence microscopy reveals that the contents of many (membrane-free)
nuclear "bodies" exchange rapidly with the soluble pool whilst the underlying
structure persists; such observations await a satisfactory biophysical
explanation. To shed light on this, we perform large-scale Brownian dynamics
simulations of a chromatin fiber interacting with an ensemble of (multivalent)
DNA-binding proteins; these proteins switch between two states -- active
(binding) and inactive (non-binding). This system provides a model for any
DNA-binding protein that can be modified post-translationally to change its
affinity for DNA (e.g., like the phosphorylation of a transcription factor).
Due to this out-of-equilibrium process, proteins spontaneously assemble into
clusters of self-limiting size, as individual proteins in a cluster exchange
with the soluble pool with kinetics like those seen in photo-bleaching
experiments. This behavior contrasts sharply with that exhibited by
"equilibrium", or non-switching, proteins that exist only in the binding state;
when these bind to DNA non-specifically, they form clusters that grow
indefinitely in size. Our results point to post-translational modification of
chromatin-bridging proteins as a generic mechanism driving the self-assembly of
highly dynamic, non-equilibrium, protein clusters with the properties of
nuclear bodies. Such active modification also reshapes intra-chromatin contacts
to give networks resembling those seen in topologically-associating domains, as
switching markedly favors local (short-range) contacts over distant ones.
