Studying the functional conservation of cis-regulatory modules and their transcriptional output

Bauer, Denis C. and Bailey, Timothy L. (2008) Studying the functional conservation of cis-regulatory modules and their transcriptional output. BMC Bioinformatics, 9 Article Number: 220. doi:10.1186/1471-2105-9-220


Author Bauer, Denis C.
Bailey, Timothy L.
Title Studying the functional conservation of cis-regulatory modules and their transcriptional output
Journal name BMC Bioinformatics   Check publisher's open access policy
ISSN 1471-2105
Publication date 2008-04-29
Year available 2008
Sub-type Article (original research)
DOI 10.1186/1471-2105-9-220
Open Access Status DOI
Volume 9
Start page Article Number: 220
Total pages 14
Place of publication London
Publisher BioMed Central
Language eng
Subject C1
060405 Gene Expression (incl. Microarray and other genome-wide approaches)
970106 Expanding Knowledge in the Biological Sciences
Formatted abstract
Background
Cis-regulatory modules (CRMs) are distinct, genomic regions surrounding the target gene that can independently activate the promoter to drive transcription. The activation of a CRM is controlled by the binding of a certain combination of transcription factors (TFs). It would be of great benefit if the transcriptional output mediated by a specific CRM could be predicted. Of equal benefit would be identifying in silico a specific CRM as the driver of the expression in a specific tissue or situation. We extend a recently developed biochemical modeling approach to manage both prediction tasks. Given a set of TFs, their protein concentrations, and the positions and binding strengths of each of the TFs in a putative CRM, the model predicts the transcriptional output of the gene. Our approach predicts the location of the regulating CRM by using predicted TF binding sites in regions near the gene as input to the model and searching for the region that yields a predicted transcription rate most closely matching the known rate.
Results
Here we show the ability of the model on the example of one of the CRMs regulating the eve gene, MSE2. A model trained on the MSE2 in D. melanogaster was applied to the surrounding sequence of the eve gene in seven other Drosophila species. The model successfully predicts the correct MSE2 location and output in six out of eight Drosophila species we examine.
Conclusion
The model is able to generalize from D. melanogaster to other Drosophila species and accurately predicts the location and transcriptional output of MSE2 in those species. However, we also show that the current model is not specific enough to function as a genome-wide CRM scanner, because it incorrectly predicts other genomic regions to be MSE2s.
Keyword Drosophila-melanogaster
Gene
Q-Index Code C1
Q-Index Status Confirmed Code
Additional Notes © 2008 Bauer and Bailey; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2009 Higher Education Research Data Collection
Institute for Molecular Bioscience - Publications
 
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Created: Tue, 07 Apr 2009, 01:28:34 EST by Cody Mudgway on behalf of Institute for Molecular Bioscience