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Control and signal processing by transcriptional interference
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
 
ID 961798
Author(s) Buetti-Dinh, Antoine; Ungricht, Rosemarie; Kelemen, János Z.; Shetty, Chetak; Ratna, Prasuna; Becskei, Attila
Author(s) at UniBasel Becskei, Attila
Year 2009
Title Control and signal processing by transcriptional interference
Journal Molecular Systems Biology
Volume 5
Pages / Article-Number 300
Mesh terms Binding, Competitive; DNA, genetics; Flow Cytometry; Gene Expression; Gene Expression Regulation, Fungal; Genome, Fungal; Kinetics; Models, Genetic; Promoter Regions, Genetic; Protein Structure, Tertiary; Saccharomyces cerevisiae, genetics; Signal Transduction; Systems Biology; Transcription, Genetic; Transcriptional Activation
Abstract A transcriptional activator can suppress gene expression by interfering with transcription initiated by another activator. Transcriptional interference has been increasingly recognized as a regulatory mechanism of gene expression. The signals received by the two antagonistically acting activators are combined by the polymerase trafficking along the DNA. We have designed a dual-control genetic system in yeast to explore this antagonism systematically. Antagonism by an upstream activator bears the hallmarks of competitive inhibition, whereas a downstream activator inhibits gene expression non-competitively. When gene expression is induced weakly, the antagonistic activator can have a positive effect and can even trigger paradoxical activation. Equilibrium and non-equilibrium models of transcription shed light on the mechanism by which interference converts signals, and reveals that self-antagonism of activators imitates the behavior of feed-forward loops. Indeed, a synthetic circuit generates a bell-shaped response, so that the induction of expression is limited to a narrow range of the input signal. The identification of conserved regulatory principles of interference will help to predict the transcriptional response of genes in their genomic context.
Publisher EMBO
ISSN/ISBN 1744-4292
edoc-URL http://edoc.unibas.ch/46407/
Full Text on edoc Available
Digital Object Identifier DOI 10.1038/msb.2009.61
PubMed ID http://www.ncbi.nlm.nih.gov/pubmed/19690569
ISI-Number WOS:000275390100010
Document type (ISI) Journal Article
 
   

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