Control and signal processing by transcriptional interference

Abstract

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.

Keywords

• noncoding transcription
• promoter
• repression