Features of developmental enhancers revealed by evolutionary processes in fish genomes: a computational and functional genomics approach

The loci of developmental transcriptional regulators are spanned by arrays of ultraconserved regulatory elements (UCRs), many of which exhibit high similarity across all vertebrates. This project aims to develop computational approaches for the generation of hypotheses about the function of those regulatory elements that can be tested in zebrafish as a model system. We will therefore focus on the evolutionary events that occurred in the fish genomes (tetraploidization, rediploidization, compaction) and th eir consequences on the conservation and genomic organization of UCRs. First, we propose to investigate potential function of UCRs that are differentially preserved between pairs of paralogs that originated in the tetraploidization event in teleost line age by comparing the expression patterns of the paralogs and assigning possible differences to UCRs preserved in only one of them. Second, we want to study the function and genomic organization of those UCRs that were lost in the genome compaction process that occur in the lineage leading to other fish model organisms (fugu, Tetraodon, medaka). Finally, based on the new classification of core promoters derived from the results of genome-wide determination of transcription start sites in the human and mous e genomes conducted by the FANTOM3 international consortium, we want to associate the fundamental differences in structures of transcription start sites with the responsiveness of genes to long-range enhancers. Selected computationally derived hypotheses will be experimentally tested in zebrafish by Tom Becker?s group at the Sars International Centre for Marine Molecular Biology. The structures of core promoters and expression patterns of selected genes and UCRs in mammalian systems will be studied in col laboration with RIKEN Genome Sciences Centre (Yokohama, Japan) and developmental neurobiologists from Karolinska Institutet (Stockholm, Sweden).