Article (Scientific journals)
Dynamic cumulative activity of transcription factors as a mechanism of quantitative gene regulation.
HE, Feng; Buer, Jan; Zeng, An-Ping et al.
2007In Genome Biology, 8 (9), p. 181
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Keywords :
Algorithms; Amino Acid Motifs; Binding Sites; Biotechnology/methods; Cell Cycle; False Positive Reactions; Fungal Proteins/metabolism; Gene Expression Regulation, Fungal; Genes, Fungal; Models, Genetic; Models, Theoretical; Saccharomyces cerevisiae/genetics; Transcription Factors/metabolism; Transcription, Genetic
Abstract :
[en] BACKGROUND: The regulation of genes in multicellular organisms is generally achieved through the combinatorial activity of different transcription factors. However, the quantitative mechanisms of how a combination of transcription factors controls the expression of their target genes remain unknown. RESULTS: By using the information on the yeast transcription network and high-resolution time-series data, the combinatorial expression profiles of regulators that best correlate with the expression of their target genes are identified. We demonstrate that a number of factors, particularly time-shifts among the different regulators as well as conversion efficiencies of transcription factor mRNAs into functional binding regulators, play a key role in the quantification of target gene expression. By quantifying and integrating these factors, we have found a highly significant correlation between the combinatorial time-series expression profile of regulators and their target gene expression in 67.1% of the 161 known yeast three-regulator motifs and in 32.9% of 544 two-regulator motifs. For network motifs involved in the cell cycle, these percentages are much higher. Furthermore, the results have been verified with a high consistency in a second independent set of time-series data. Additional support comes from the finding that a high percentage of motifs again show a significant correlation in time-series data from stress-response studies. CONCLUSION: Our data strongly support the concept that dynamic cumulative regulation is a major principle of quantitative transcriptional control. The proposed concept might also apply to other organisms and could be relevant for a wide range of biotechnological applications in which quantitative gene regulation plays a role.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
HE, Feng 
Buer, Jan
Zeng, An-Ping
BALLING, Rudi ;  Helmholtz Centre for Infection Research, Inhoffenstraße, Braunschweig, Germany
Language :
Title :
Dynamic cumulative activity of transcription factors as a mechanism of quantitative gene regulation.
Publication date :
Journal title :
Genome Biology
Publisher :
Springer, London, United Kingdom
Volume :
Issue :
Pages :
Peer reviewed :
Peer Reviewed verified by ORBi
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