Enhancer topology and remote operation

In this second lecture, Pr Denis Duboule describes original approaches involving enhancer traps, first in Drosophila flies using the P element as a vector, then in mice via the embryonic stem (ES) cell route. It then shows how the main detection tool (the lacZ gene) was integrated into these experimental strategies, and how these approaches have evolved to lead to current, more efficient strategies for discovering enhancers present within a pre-determined regulatory landscape. The question then arises of how to associate a particular enhancer with one or more target genes, and the importance of this problem is illustrated by a particularly telling case: the presence of an enhancer of the " gremlin "gene inside a neighbouring gene, causing a situation that remained confusing for many years before being resolved.