%0 Journal Article %T Comparative genomics of Drosophila and human core promoters %A Peter C FitzGerald %A David Sturgill %A Andrey Shyakhtenko %A Brian Oliver %A Charles Vinson %J Genome Biology %D 2006 %I BioMed Central %R 10.1186/gb-2006-7-7-r53 %X We determined the distribution of all 65,536 octamer (8-mers) DNA sequences in 10,914 Drosophila promoters and two sets of human promoters aligned relative to the transcriptional start site. In Drosophila, 298 8-mers have highly significant (p ¡Ü 1 ¡Á 10-16) non-random distributions peaking within 100 base-pairs of the transcriptional start site. These sequences were grouped into 15 DNA motifs. Ten motifs, termed directional motifs, occur only on the positive strand while the remaining five motifs, termed non-directional motifs, occur on both strands. The only directional motifs to localize in human promoters are TATA, INR, and DPE. The directional motifs were further subdivided into those precisely positioned relative to the transcriptional start site and those that are positioned more loosely relative to the transcriptional start site. Similar numbers of non-directional motifs were identified in both species and most are different. The genes associated with all 15 DNA motifs, when they occur in the peak, are enriched in specific Gene Ontology categories and show a distinct mRNA expression pattern, suggesting that there is a core promoter code in Drosophila.Drosophila and human promoters use different DNA sequences to regulate gene expression, supporting the idea that evolution occurs by the modulation of gene regulation.The regulation of eukaryotic gene expression is a complex process involving many different control mechanisms, including chromatin structure and DNA sequences that bind specific proteins [1]. For convenience, we divide DNA sequence motifs that are bound by proteins into three distinct classes: the core promoter region where the basal transcription machinery binds; motifs within the core promoter region that bind to transcription factors; and classic enhancer or silencer motifs, that function at large distances from the transcriptional start site (TSS). Two extremes of regulated gene expression may be envisioned. In one extreme, the general transcript %U http://genomebiology.com/2006/7/7/R53