Control and signal processing by transcriptional interference.
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.
Buetti-Dinh
Antoine
A
Institute of Molecular Biology, University of Zurich, Zurich, Switzerland.
Ungricht
Rosemarie
R
Kelemen
János Z
JZ
Shetty
Chetak
C
Ratna
Prasuna
P
Becskei
Attila
A
D001667:Binding, Competitive; D004247:DNA / Q000235:genetics; D005434:Flow Cytometry; D015870:Gene Expression; D015966:Gene Expression Regulation, Fungal; D016681:Genome, Fungal; D007700:Kinetics; D008957:Models, Genetic; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000235:genetics; D015398:Signal Transduction; D049490:Systems Biology; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D004247:DNA
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