Recent work by Matthew Ronshaugen and Mike Levine shows that interactions between enhancers and promoters most probably involve looping of the intervening DNA. The authors, who were studying the fruitfly Drosophila melanogaster, discovered this by using an experimental approach that allowed them to directly observe interactions in trans between homologous chromosomes.

To examine long range enhancer–promoter interactions, Ronshaugen and Levine focused on the well-characterized Abdominal-B (Abd-B) locus and one of its enhancers, IAB5, which maps approximately 50 kb from the Abd-B promoter. Because the IAB5 enhancer sequence is transcribed — a feature that might be common to many enhancer elements — the authors used RNA fluorescent in situ hybridization (FISH) to examine its interaction with the Abd-B promoter.

Confocal microscopy of D. melanogaster embryo abdominal segments — where Abd-B is normally expressed — also revealed that enhancer and promoter sequences frequently interact with each other; the micrographs suggest that the intervening DNA loops out. Differently coloured foci of enhancer and promoter transcription were partially overlapping, indicating that at least some of the interactions might be direct.

A surprise bonus result awaited the authors among their data. Confocal images revealed frequent interactions between the enhancers and promoters of homologous loci. Such interactions, visualized here for the first time, are the molecular basis for transvection — a genetic phenomenon first described in flies, whereby some regulatory mutations can be complemented in trans by a homologous sequence. A specific sequence element in the 3′ region of Abd-B is known to mediate this somatic pairing of homologues — the authors suggest that such elements might exist upstream of many genes and that transvection might be an important general mechanism for gene regulation in higher Metazoa.