Lessons on gene regulation learnt from the Drosophila melanogaster bithorax complex

Homeotic or Hox genes determine the anterior-posterior body axis in all bilaterians. As expected, Hox genes are highly conserved across bilaterians. Interestingly, however, the peculiar organization of Hox genes in the form of clusters where the order of occurrence of genes in the genome corresponds to the order in which they regulate segmental identity of anterior-posterior body axis is also conserved. The relation between collinearity of arrangement of genes on the chromosomes and spatial function along the body axis has attracted attention to exploring its relevance in the precise regulation of Hox genes. Conservation of genes and their arrangement suggests a linkage between co-regulation and the higher order chromatin organization of the entire complex. To this end, we and others have used Drosophila as the model system to understand the cis-and trans-regulatory components of Hox genes. A number of chromatin-level regulatory elements, like chromatin domain boundaries, and Polycomb Response Elements (PREs) have been discovered in this process. Interestingly, much of what has emerged from the study of homeotic genes, the cis-elements and protein factors, have relevance across the genome in a large number of regulatory events beyond the Hox genes. Here, we review our findings and discuss their genome-wide implications in complex regulatory processes.