Large-scale discovery of promoter motifs in Drosophila melanogaster.

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...

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Main Authors: Thomas A Down, Casey M Bergman, Jing Su, Tim J P Hubbard
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2007-01-01
Series:PLoS Computational Biology
Online Access:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.0030007&type=printable
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author Thomas A Down
Casey M Bergman
Jing Su
Tim J P Hubbard
author_facet Thomas A Down
Casey M Bergman
Jing Su
Tim J P Hubbard
author_sort Thomas A Down
collection DOAJ
description 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.
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spelling doaj-art-16e6c3a73f614bd1a41ef315e274f0ae2025-08-20T02:00:47ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582007-01-0131e710.1371/journal.pcbi.0030007Large-scale discovery of promoter motifs in Drosophila melanogaster.Thomas A DownCasey M BergmanJing SuTim J P HubbardA 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.https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.0030007&type=printable
spellingShingle Thomas A Down
Casey M Bergman
Jing Su
Tim J P Hubbard
Large-scale discovery of promoter motifs in Drosophila melanogaster.
PLoS Computational Biology
title Large-scale discovery of promoter motifs in Drosophila melanogaster.
title_full Large-scale discovery of promoter motifs in Drosophila melanogaster.
title_fullStr Large-scale discovery of promoter motifs in Drosophila melanogaster.
title_full_unstemmed Large-scale discovery of promoter motifs in Drosophila melanogaster.
title_short Large-scale discovery of promoter motifs in Drosophila melanogaster.
title_sort large scale discovery of promoter motifs in drosophila melanogaster
url https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.0030007&type=printable
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AT jingsu largescalediscoveryofpromotermotifsindrosophilamelanogaster
AT timjphubbard largescalediscoveryofpromotermotifsindrosophilamelanogaster