Quantitative analysis of the transcription control mechanism

Abstract

Gene transcription requires a sequence of promoter state transitions, including chromatin remodeling, assembly of the transcription machinery, and clearance of the promoter by RNA polymerase. The rate-limiting steps in this sequence are regulated by transcriptional activators that bind at specific promoter elements. As the transition kinetics of individual promoters cannot be observed, the identity of the activator-controlled steps has remained a matter of speculation. In this study, we investigated promoter chromatin structure, and the intrinsic noise of expression over a wide range of expression values for the PHO5 gene of yeast. Interpretation of our results with regard to a stochastic model of promoter chromatin remodeling and gene expression suggests that the regulatory architecture of the gene expression process is measurably reflected in its intrinsic noise profile. Our chromatin structure and noise analyses indicate that the activator of PHO5 transcription stimulates the rates of promoter nucleosome disassembly, and assembly of the transcription machinery after nucleosome removal, but no other rates of the expression process.