Promoter architecture dictates cell-to-cell variability in gene expression

Area of Science:

• Molecular Biology
• Systems Biology
• Genetics

Background:

• Cell-to-cell variability in gene expression is a key area in gene regulation research.
• A gap exists between theoretical models of prokaryotic transcriptional regulation and experimental findings regarding expression variability.
• Existing studies suggest variability is independent of regulatory architecture, contradicting some molecular models.

Purpose of the Study:

• To investigate the relationship between molecular details of transcription and gene expression variability in Escherichia coli.
• To determine if gene expression variability is influenced by promoter strength, transcription factor binding, and transcription factor copy numbers.
• To test whether parameter-free models can predict observed gene expression variability.

Main Methods:

• Systematic construction of Escherichia coli promoters with varied strengths and transcription factor binding characteristics.
• Utilizing messenger RNA (mRNA) fluorescence in situ hybridization to quantify gene expression variability.
• Comparing experimental data with predictions from parameter-free molecular models.

Main Results:

• Gene expression variability was found to be dependent on the molecular details of transcription.
• Systematic variations in promoter and transcription factor parameters directly affected mRNA expression variability.
• Parameter-free models accurately predicted the experimentally observed variability in gene expression.

Conclusions:

• The molecular mechanisms governing transcription directly dictate variability in mRNA expression.
• Transcriptional noise is a tunable parameter, suggesting it can be shaped by evolutionary processes.
• Gene expression variability is not indifferent to the underlying regulatory architecture but is precisely controlled by transcriptional details.