Enhancers can be many tens of kilobases away from the promoters they bind to, but what regulates these interactions? In this issue, two papers shed light on the mechanisms that control enhancer-promoter (E-P)communication.
On , Judith Kassis and co-workers reveal that at the Drosophila engrailed(en) locus, which is regulated by multiple enhancers, at least three different mechanisms enable context-specific E-P interactions. Using transposable elements that contain en promoter sequences and that preferentially insert near the en gene (a phenomenon known as homing), the authors show that, for one set of enhancers involved in early embryogenesis, the en promoter sequence itself is necessary for E-P interactions. By contrast, the interaction of the later-acting imaginal disc enhancers with the en promoter depends on sequences - termed tethering elements - that lie near the promoter. Finally, long-range en E-P interactions require the combined presence of the enpromoter and neighbouring Polycomb-group response elements (PREs). The authors speculate that other genes with extensive regulatory regions might also employ multiple, context-dependent mechanisms to achieve E-P interaction specificity.
On , James Jaynes and colleagues report that the region between the Drosophilagenes even skipped (eve) and TER94 blocks enhancers(displaying so-called insulator activity) and also mediates the homing of eve promoter-containing transgenes to the eve-TER94genomic region. Even when localised to a 600 bp sequence, these two activities cannot be separated, indicating that they are functionally linked. Interestingly, homed eve promoter-containing transgenes respond to endogenous eve enhancers from distances as far away as 3300 kb. This extremely long-range E-P communication depends on both the insulator/homing sequence and the eve promoter, similar to the combinatorial effect of en promoters and PREs on en E-P interaction specificity reported by Judith Kassis and co-workers. These data have far-reaching implications for how insulators might regulate E-P communication.
An additional study, by Michael Levine and co-workers (see ), indicates that naturally occurring variations in the interaction of conserved enhancers with different target genes might contribute to the evolutionary diversification of insect species. Together, these findings highlight the importance and complexity of E-P communications in the tightly controlled process of development.
