Long-distance regulatory interactions between enhancers and their target
genes are commonplace in higher eukaryotes. Interposed boundaries or insulators
are able to block these long distance regulatory interactions. The mechanistic
basis for insulator activity and how it relates to enhancer
action-at-a-distance remains unclear. Here we explore the idea that topological
loops could simultaneously account for regulatory interactions of distal
enhancers and the insulating activity of boundary elements. We show that while
loop formation is not in itself sufficient to explain action at a distance,
incorporating transient non-specific and moderate attractive interactions
between the chromatin fibers strongly enhances long-distance regulatory
interactions and is sufficient to generate a euchromatin-like state. Under
these same conditions, the subdivision of the loop into two topologically
independent loops by insulators inhibits inter-domain interactions. The
underlying cause of this effect is a suppression of crossings in the contact
map at intermediate distances. Thus our model simultaneously accounts for
regulatory interactions at a distance and the insulator activity of boundary
elements. This unified model of the regulatory roles of chromatin loops makes
several testable predictions that could be confronted with \emph{in vitro}
experiments, as well as genomic chromatin conformation capture and fluorescent
microscopic approaches.Comment: 10 pages, originally submitted to an (undisclosed) journal in May
201
