A rationale for the enhanceosome and other evolutionarily constrained enhancers

Metazoan enhancers direct localized stripes, bands and cell-specific patterns of gene expression during development (for example [1]). A typical enhancer is a 500 base pair DNA segment that contains clustered binding sites for two or more sequence-specific transcription factors. Roughly half of all enhancers are located somewhere in the 5′ flanking region of the associated transcription unit, while the other half are distributed among introns, 3′ flanking regions or even protein-coding sequences (for example [2]). Bioinformatics studies suggest that enhancers usually contain a flexible arrangement of binding sites (for example [3]). Here, we present a model to explain why a special subset of enhancers contains a fixed organization.