François Karch

Although it is now possible to engineer living organisms to express almost any gene in a controlled fashion, the mechanisms governing this control still remain elusive. In eukaryotes, genes are large, with regulatory elements often tens, or even hundreds of kilobases away from their target promoter. Yet, even given this distance, these distal elements can still faithfully find and control their target promoter in a precise fashion. The experiments performed in our laboratory aim at understanding on how these distal regulatory elements can control gene expression. As our model system, we study the regulation of the homeotic genes (Hox gene) of the Drosophila bithorax complex (BX-C) Regulatory elements, spanning a 300 kilobases-long region of the BX-C DNA are required for proper expression of three hox genes, Ubx, abd-A and Abd-B. Homeotic genes are strikingly conserved between invertebrates and vertebrates. The genes are found in clusters or 'complexes' that are arranged on the chromosome in the order of their function along the anteroposterior body axis. This striking correspondence between genomic organization and antero-posterior axis gives us a unique opportunity to study gene regulation in its chromosomal context. The amazing evolutionary conservation in the genomic organization of hox complexes is further highlighted by the recent finding of 2 conserved micro-RNAs at similar location within the complexes of arthropods and vertebrates.