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Inferring condition-specific modulation of transcription factor activity in yeast through regulon-based analysis of genomewide expression
- Source :
- PLoS ONE, Vol 3, Iss 9, p e3112 (2008), PLoS ONE, PLoS ONE, 3(9). Public Library of Science
- Publication Year :
- 2008
-
Abstract
- Background: A key goal of systems biology is to understand how genomewide mRNA expression levels are controlled by transcription factors (TFs) in a condition-specific fashion. TF activity is frequently modulated at the post-translational level through ligand binding, covalent modification, or changes in sub-cellular localization. In this paper, we demonstrate how prior information about regulatory network connectivity can be exploited to infer condition-specific TF activity as a hidden variable from the genomewide mRNA expression pattern in the yeast Saccharomyces cerevisiae.Methodology/Principal Findings: We first validate experimentally that by scoring differential expression at the level of gene sets or "regulons" comprised of the putative targets of a TF, we can accurately predict modulation of TF activity at the post-translational level. Next, we create an interactive database of inferred activities for a large number of TFs across a large number of experimental conditions in S. cerevisiae. This allows us to perform TF-centric analysis of the yeast regulatory network.Conclusions/Significance: We analyze the degree to which the mRNA expression level of each TF is predictive of its regulatory activity. We also organize TFs into "co-modulation networks" based on their inferred activity profile across conditions, and find that this reveals functional and mechanistic relationships. Finally, we present evidence that the PAC and rRPE motifs antagonize TBP-dependent regulation, and function as core promoter elements governed by the transcription regulator NC2. Regulon-based monitoring of TF activity modulation is a powerful tool for analyzing regulatory network function that should be applicable in other organisms. Tools and results are available online at http://bussemakerlab.org/RegulonProfiler/.
- Subjects :
- Saccharomyces cerevisiae Proteins
Transcription, Genetic
Systems biology
Green Fluorescent Proteins
Saccharomyces cerevisiae
Gene Expression
Computational Biology/Transcriptional Regulation
lcsh:Medicine
Models, Biological
Regulon
Cell Physiological Phenomena
03 medical and health sciences
0302 clinical medicine
Gene Expression Regulation, Fungal
Transcriptional regulation
RNA, Messenger
Promoter Regions, Genetic
lcsh:Science
Transcription factor
030304 developmental biology
Genetics
Regulation of gene expression
0303 health sciences
Computational Biology/Systems Biology
Multidisciplinary
Models, Genetic
biology
Genetics and Genomics/Functional Genomics
lcsh:R
Promoter
Genetics and Genomics/Bioinformatics
biology.organism_classification
Microscopy, Fluorescence
Computational Biology/Sequence Motif Analysis
lcsh:Q
Genome, Fungal
030217 neurology & neurosurgery
Function (biology)
Transcription Factors
Research Article
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 3
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....773ebb5cae6eb3b5c490dc2526f5d0fe