Large-scale discovery of promoter motifs in Drosophila melanogaster

• Published in: PLoS computational biology Vol. 3; no. 1; p. e7
• Main Authors: Down, Thomas A, Bergman, Casey M, Su, Jing, Hubbard, Tim J P
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01-01-2007; Public Library of Science (PLoS)
• Subjects: Amino Acid Motifs; Animals; Base Sequence; Bias; Binding Sites; Chromosome Mapping - methods; Computational Biology; Developmental Biology; Drosophila; Drosophila melanogaster; Drosophila melanogaster - embryology; Drosophila melanogaster - genetics; Drosophila Proteins - genetics; Gene expression; Genetic aspects; Genetic regulation; Genetic transcription; Genetics; Molecular Sequence Data; Promoter Regions, Genetic - genetics; Promoters (Genetics); Protein Binding; Proteins; Sequence Analysis, DNA - methods; Transcription Factors - genetics; United States; Drosophila Proteins; Promoter Regions, Genetic; Animals; Base Sequence; Molecular Sequence Data; Protein Binding; Chromosome Mapping; Transcription Factors; Binding Sites; Drosophila melanogaster; Sequence Analysis, DNA; Amino Acid Motifs
• ISSN: 1553-7358; 1553-734X; 1553-7358
• DOI: 10.1371/journal.pcbi.0030007

A key step in understanding gene regulation is to identify the repertoire of transcription factor binding motifs (TFBMs) that form the building blocks of promoters and other regulatory elements. Identifying these experimentally is very laborious, and the number of TFBMs discovered remains relatively small, especially when compared with the hundreds of transcription factor genes predicted in metazoan genomes. We have used a recently developed statistical motif discovery approach, NestedMICA, to detect candidate TFBMs from a large set of Drosophila melanogaster promoter regions. Of the 120 motifs inferred in our initial analysis, 25 were statistically significant matches to previously reported motifs, while 87 appeared to be novel. Analysis of sequence conservation and motif positioning suggested that the great majority of these discovered motifs are predictive of functional elements in the genome. Many motifs showed associations with specific patterns of gene expression in the D. melanogaster embryo, and we were able to obtain confident annotation of expression patterns for 25 of our motifs, including eight of the novel motifs. The motifs are available through Tiffin, a new database of DNA sequence motifs. We have discovered many new motifs that are overrepresented in D. melanogaster promoter regions, and offer several independent lines of evidence that these are novel TFBMs. Our motif dictionary provides a solid foundation for further investigation of regulatory elements in Drosophila, and demonstrates techniques that should be applicable in other species. We suggest that further improvements in computational motif discovery should narrow the gap between the set of known motifs and the total number of transcription factors in metazoan genomes.