title: Precise regulation of gene expression dynamics favors complex promoter architectures.
abstract: Promoters process signals through recruitment of transcription factors and RNA polymerase, and dynamic changes in promoter activity constitute a major noise source in gene expression. However, it is barely understood how complex promoter architectures determine key features of promoter dynamics. Here, we employ prototypical promoters of yeast ribosomal protein genes as well as simplified versions thereof to analyze the relations among promoter design, complexity, and function. These promoters combine the action of a general regulatory factor with that of specific transcription factors, a common motif of many eukaryotic promoters. By comprehensively analyzing stationary and dynamic promoter properties, this model-based approach enables us to pinpoint the structural characteristics underlying the observed behavior. Functional tradeoffs impose constraints on the promoter architecture of ribosomal protein genes. We find that a stable scaffold in the natural design results in low transcriptional noise and strong co-regulation of target genes in the presence of gene silencing. This configuration also exhibits superior shut-off properties, and it can serve as a tunable switch in living cells. Model validation with independent experimental data suggests that the models are sufficiently realistic. When combined, our results offer a mechanistic explanation for why specific factors are associated with low protein noise in vivo. Many of these findings hold for a broad range of model parameters and likely apply to other eukaryotic promoters of similar structure.
authors.affiliation: Department of Biosystems Science and Engineering and Swiss Institute of Bioinformatics, ETH Zurich, Basel, Switzerland.
authors.forename: Dirk
authors.initials: D
authors.lastname: Müller
authors.forename: Jörg
authors.initials: J
authors.lastname: Stelling
mesh_terms: D004271:DNA, Fungal / Q000737:chemistry / Q000235:genetics; D003627:Data Interpretation, Statistical; D005583:Fourier Analysis; D015966:Gene Expression Regulation, Fungal; D016014:Linear Models; D008957:Models, Genetic; D017711:Nonlinear Dynamics; D009690:Nucleic Acid Conformation; D011401:Promoter Regions, Genetic / Q000502:physiology*; D015203:Reproducibility of Results; D012269:Ribosomal Proteins / Q000235:genetics* / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology*
chemical_list: D004271:DNA, Fungal; D012269:Ribosomal Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors