Tuning and controlling gene expression noise in synthetic gene networks
| Autor: | Rhys M. Adams, Gábor Balázsi, Kevin F. Murphy, Xiao Wang, James J. Collins |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Saccharomyces cerevisiae Proteins
Transcription Genetic TATA box Gene regulatory network Saccharomyces cerevisiae Computational biology Biology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Gene expression Genes Synthetic Genetics Gene Regulatory Networks TetR Gene 030304 developmental biology Regulation of gene expression 0303 health sciences TATA Box Noise Gene Expression Regulation chemistry Mutation Synthetic Biology and Chemistry Trans-Activators 030217 neurology & neurosurgery |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 0305-1048 |
| DOI: | 10.1093/nar/gkq091 |
| Popis: | Synthetic gene networks can be used to control gene expression and cellular phenotypes in a variety of applications. In many instances, however, such networks can behave unreliably due to gene expression noise. Accordingly, there is a need to develop systematic means to tune gene expression noise, so that it can be suppressed in some cases and harnessed in others, e.g. in cellular differentiation to create population-wide heterogeneity. Here, we present a method for controlling noise in synthetic eukaryotic gene expression systems, utilizing reduction of noise levels by TATA box mutations and noise propagation in transcriptional cascades. Specifically, we introduce TATA box mutations into promoters driving TetR expression and show that these mutations can be used to effectively tune the noise of a target gene while decoupling it from the mean, with negligible effects on the dynamic range and basal expression. We apply mathematical and computational modeling to explain the experimentally observed effects of TATA box mutations. This work, which highlights some important aspects of noise propagation in gene regulatory cascades, has practical implications for implementing gene expression control in synthetic gene networks. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|