ArticleGenome research2014
Probing the effect of promoters on noise in gene expression using thousands of designed sequences.
Article in Genome research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 127 citations in OpenAlex.
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- Deep-learning-assisted Sort-Seq enables high-throughput profiling of gene expression characteristics with high precision.Science advances · 2023Article
- Lola-I is a promoter pioneer factor that establishes de novo Pol II pausing during development.Nature communications · 2023Article
- Multidimensional characterization of inducible promoters and a highly light-sensitive LOV-transcription factor.Nature communications · 2023Article
- Contributions of mutation and selection to regulatory variation: lessons from thePhilosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Deep Mutational Scanning of an Oxygen-Independent Fluorescent Protein CreiLOV for Comprehensive Profiling of Mutational and Epistatic Effects.ACS synthetic biology · 2023Article
- Being noisy in a crowd: Differential selective pressure on gene expression noise in model gene regulatory networks.PLoS computational biology · 2023Article
- The minimal intrinsic stochasticity of constitutively expressed eukaryotic genes is sub-Poissonian.bioRxiv : the preprint server for biology · 2023Article
- Enhanced Transcriptional Strength of HIV-1 Subtype C Minimizes Gene Expression Noise and Confers Stability to the Viral Latent State.Journal of virology · 2023Article
- Navigating Environmental Transitions: the Role of Phenotypic Variation in Bacterial Responses.mBio · 2022Review
- Transcription factor binding process is the primary driver of noise in gene expression.PLoS genetics · 2022Article
- Controlling gene expression with deep generative design of regulatory DNA.Nature communications · 2022Article
- Elucidation of Sequence-Function Relationships for an Improved BiobutanolFrontiers in bioengineering and biotechnology · 2022Article
- Genome-wide gene expression noise in Escherichia coli is condition-dependent and determined by propagation of noise through the regulatory network.PLoS biology · 2021Article
- A Sort-Seq Approach to the Development of Single Fluorescent Protein Biosensors.ACS chemical biology · 2021Article
14 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Genetically identical cells exhibit large variability (noise) in gene expression, with important consequences for cellular function. Although the amount of noise decreases with and is thus partly determined by the mean expression level, the extent to which different promoter sequences can deviate away from this trend is not fully known. Here, we present a high-throughput method for measuring promoter-driven noise for thousands of designed synthetic promoters in parallel. We use it to investigate how promoters encode different noise levels and find that the noise levels of promoters with similar mean expression levels can vary more than one order of magnitude, with nucleosome-disfavoring sequences resulting in lower noise and more transcription factor binding sites resulting in higher noise. We propose a kinetic model of gene expression that takes into account the nonspecific DNA binding and one-dimensional sliding along the DNA, which occurs when transcription factors search for their target sites. We show that this assumption can improve the prediction of the mean-independent component of expression noise for our designed promoter sequences, suggesting that a transcription factor target search may affect gene expression noise. Consistent with our findings in designed promoters, we find that binding-site multiplicity in native promoters is associated with higher expression noise. Overall, our results demonstrate that small changes in promoter DNA sequence can tune noise levels in a manner that is predictable and partly decoupled from effects on the mean expression levels. These insights may assist in designing promoters with desired noise levels.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.