KEITH, B.A.*; GIBSON-BROWN, J.J.; Washington University in St. Louis; Washington University in St. Louis: Computational approaches to regulatory element identification: comparative analyses of the vertebrate Eomesodermin and T-brain T-box loci

With the increasing realization that the evolution of developmental gene regulation is likely to be the driving force in the evolution of novel morphologies, the analysis of related expression patterns and their underlying regulatory elements has become increasingly important. Now that multiple vertebrate genomes are approaching a finished state, one canfinally perform comparative analyses on an evolutionary timescale. We are studying Human, Mouse, and now Fugu upstream regions of the developmental transcription factors Eomesodermin and T-brain. These genes were chosen because they have duplicated recently from one another, offering another axis of similarity to study. More importantly, T-brain has a subset of the expression of Eomesodermin, suggesting a duplication-loss of regulatory elements model. We are using comparative methods, including Pipmaker, to narrow down which putative regulatory elements are likely to be interesting, along with composition-based analyses, looking for correlations and putative elements which are over- and under-represented compared to expectations. We have found some putative regulatory elements which appear over- and under- represented, including deltaEF1 and several enhancer binding and activator proteins. Many of these are also present in similar locations among the Mouse and Human upstream sequence.