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

Authors: Bauer, Denis C.; Bailey, Timothy L.;

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

Abstract

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.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.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.

Country
Australia
Keywords

QH301-705.5, Computer applications to medicine. Medical informatics, Molecular Sequence Data, R858-859.7, 612, Regulatory Sequences, Nucleic Acid, Drosophila-melanogaster, Gene, Biochemistry, C1, Biology (General), Promoter Regions, Genetic, Molecular Biology, Conserved Sequence, Base Sequence, Chromosome Mapping, Sequence Analysis, DNA, Computer Science Applications, 970106 Expanding Knowledge in the Biological Sciences, 060405 Gene Expression (incl. Microarray and other genome-wide approaches), Algorithms, Research Article, Transcription Factors

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
9
Average
Average
Top 10%
Green
gold