Phylogenetic Shadowing in Primate Promoter Regions

( Robert Querfurth )

The identification of regulatory elements such as promoters is an important step towards a better understanding of the functional significance of differential gene expression and regulation networks.
During the last years comparative genome analysis has quickly developed into one of the most effective approaches to delineate regulatory elements. By aligning orthologous loci and determining conserved promoter regions of 4 genomes (human, mouse, rat, dog) numerous conserved motifs could be identified.

This approach termed "phylogenetic shadowing" is quite powerful, as several new and remarkably conserved motifs could be identified. However the lack of sequenced genomes of closely related mammals limits bioinformatic identification of conserved motifs to the mammalian clade. We use this phylogenetic shadowing approach in combination with RNAi and ChIP-seq experiments to identify primate and human specific regulatory elements as well as deeper conserved sequence motifs.

We focus our analysis on human chromosome 21 since it is well annotated and its genes are well studied in functional genomic approaches. The orthologous promoter regions of the ~300 genes on human chromosome 21 are being amplified for gorilla and orangutan and a representative set of 5 old- and 4 new-world monkey species.
By this approach preliminary data show lineage-specific and overall conserved motifs that might contribute to differential gene expression in distinct clades. The identified motifs will be linked to various data sets, including expression profiles, promoter predictions and gene ontology annotations, leading to a broader knowledge of promoter structures and functionality.