The loci of developmental transcriptional regulators are spanned by arrays of conserved noncoding elements (CNEs), many of which exhibit high similarity across all vertebrates. We are on the verge of discovering the fundamental involvement of these elemen ts and the genomic regions they reside in developmental processes, evolutionary resilience to chromosomal rearrangements. Based on growing amount of data and our observations, it is also likely that those regions are causally connected with many types of cancer, since most known cancer genes co-localize with CNEs. In this project we propose computational approaches to the discovery of mechanisms of regulation that take place at those elements, evolutionary pressure they exert on chromosome structure and g ene order, as well as the nature of their apparent connection with cancer-related genes. We shall take advantage of our array of collaborations to be the first to incorporate the results of new transcriptomics technologies into our analyses, and to experi mentally test our findings in zebrafish as a model organism.