Computation-Based Discovery of Related Transcriptional Regulatory Modules and Motifs Using an Experimentally Validated Combinatorial Model
Open Access
- 1 July 2002
- journal article
- research article
- Published by Cold Spring Harbor Laboratory in Genome Research
- Vol. 12 (7), 1019-1028
- https://doi.org/10.1101/gr.228902
Abstract
Gene expression is regulated by transcription factors that interact with cis-regulatory elements. Predicting these elements from sequence data has proven difficult. We describe here a successful computational search for elements that direct expression in a particular temporal-spatial pattern in the Drosophila embryo, based on a single well characterized enhancer model. The fly genome was searched to identify sequence elements containing the same combination of transcription factors as those found in the model. Experimental evaluation of the search results demonstrates that our method can correctly predict regulatory elements and highlights the importance of functional testing as a means of identifying false-positive results. We also show that the search results enable the identification of additional relevant sequence motifs whose functions can be empirically validated. This approach, combined with gene expression and phylogenetic sequence data, allows for genome-wide identification of related regulatory elements, an important step toward understanding the genetic regulatory networks involved in development.[Sequence data reported in this paper have been deposited in GenBank with accession nos. AF513981 (EveMHE) and AF513982 (Hbr DME). Supplementary material is available online at http://www.genome.org. The following individuals kindly provided reagents, samples, or unpublished information as indicated in the paper: R. Blackman]Keywords
This publication has 84 references indexed in Scilit:
- Exploiting transcription factor binding site clustering to identify cis-regulatory modules involved in pattern formation in the Drosophila genomeProceedings of the National Academy of Sciences of the United States of America, 2002
- The Genome Sequence of Drosophila melanogasterScience, 2000
- Information Content and Free Energy in DNA–Protein InteractionsJournal of Theoretical Biology, 1998
- Finding DNA regulatory motifs within unaligned noncoding sequences clustered by whole-genome mRNA quantitationNature Biotechnology, 1998
- Identification of regulatory regions which confer muscle-specific gene expressionJournal of Molecular Biology, 1998
- Gapped BLAST and PSI-BLAST: a new generation of protein database search programsNucleic Acids Research, 1997
- A novel method to develop highly specific models for regulatory units detects a new LTR in GenBank which contains a functional promoterJournal of Molecular Biology, 1997
- Sequence logos: a new way to display consensus sequencesNucleic Acids Research, 1990
- Selection of DNA binding sites by regulatory proteinsJournal of Molecular Biology, 1987
- Interspecific nucleotide sequence comparisons used to identify regulatory and structural features of the Drosophila hsp82 geneJournal of Molecular Biology, 1986