COOPERATION OF REGULATORY ELEMENTS INVOLVED IN THE ACTIVATION OF THE HOXD-11 GENE

We have used lacZ reporter gene constructs to study the cis regulation of the murine Hoxd-11 gene (previously Hox-4.6) in transgenic mice. W e identified a genomic region, which was able to simulate important as pects of the developmental regulation of the gene. A short regulatory region, located 3' to the Hoxd-11 transcription unit, was required to mimic initial activation. This regulatory region contains two stretche s of DNA, that are 'highly conserved in the chicken Hoxd-11 3' flankin g region. A chimeric construct containing these short homologous regio ns from the chicken gene could replace the complete murine fragment th us demonstrating that the conserved domains carry the main regulatory elements involved in this activation. The first half of this bipartite regulatory region has positive regulatory activity, while the second half is required to restrict gene expression to the proper posterior d omain in the somitic mesoderm. Our results suggest that the control of the Hoxd-11 promoter involves tissue-specific cooperations between re gulatory elements.