Comparative genomics of Drosophila and human core promoters

Peter C FitzGerald¹ , David Sturgill² , Andrey Shyakhtenko³ , Brian Oliver² and Charles Vinson³

¹Genome Analysis Unit, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA

²Laboratory of Cellular and Developmental Biology National Institute of Diabetes and Digestive and Kidney, National Institutes of Health, Bethesda, MD 20892, USA

³Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA

author email corresponding author email

Genome Biology 2006, 7:R53doi:10.1186/gb-2006-7-7-r53


Published:	7 July 2006

Subject areas: Molecular biology, Genome studies, Bioinformatics, Biochemistry and structural biology

Abstract

Background

The core promoter region plays a critical role in the regulation of eukaryotic gene expression. We have determined the non-random distribution of DNA sequences relative to the transcriptional start site in Drosophila melanogaster promoters to identify sequences that may be biologically significant. We compare these results with those obtained for human promoters.

Results

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 ≤ 1 × 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.

Conclusion

Drosophila and human promoters use different DNA sequences to regulate gene expression, supporting the idea that evolution occurs by the modulation of gene regulation.