g3journal | Enhancers physically interact with transcriptional promoters, looping
over distances that can span multiple regulatory elements.
Given that enhancer-promoter (EP) interactions
generally occur via common protein complexes, it is unclear whether EP
pairing
is predominantly deterministic or proximity guided.
Here we present cross-organismic evidence suggesting that most EP pairs
are compatible, largely determined by physical
proximity rather than specific interactions. By re-analyzing
transcriptome
datasets, we find that the transcription of gene
neighbors is correlated over distances that scale with genome size. We
experimentally
show that non-specific EP interactions can explain
such correlation, and that EP distance acts as a scaling factor for the
transcriptional influence of an enhancer. We
propose that enhancer sharing is commonplace among eukaryotes, and that
EP distance
is an important layer of information in gene
regulation.
