Complex organizational structure of the genome revealed by genome-wide analysis of single and alternative promoters in Drosophila melanogaster.

backgroundThe promoter is a critical necessary transcriptional cis-regulatory element. In addition to its role as an assembly site for the basal transcriptional apparatus, the promoter plays a key part in mediating temporal and spatial aspects of gene expression through differential binding of transcription factors and selective interaction with distal enhancers. Although many genes have multiple promoters, little attention has been focused on how these relate to one another; nor has much study been directed at relationships between promoters of adjacent genes.

resultsWe have undertaken a systematic investigation of Drosophila promoters. We divided promoters into three groups: unique promoters, first alternative promoters (the most 5' of a gene's multiple promoters), and downstream alternative promoters (the remaining alternative promoters 3' to the first). We observed distinct nucleotide distribution and sequence motif preferences among these three classes. We also investigated the promoters of neighboring genes and found that a greater than expected number of adjacent genes have similar sequence motif profiles, which may allow the genes to be regulated in a coordinated fashion. Consistent with this, there is a positive correlation between similar promoter motifs and related gene expression profiles for these genes.

conclusionsOur results suggest that different regulatory mechanisms may apply to each of the three promoter classes, and provide a mechanism for "gene expression neighborhoods," local clusters of co-expressed genes. As a whole, our data reveal an unexpected complexity of genomic organization at the promoter level with respect to both alternative and neighboring promoters.