ArticleeLife2022
Promoter sequence and architecture determine expression variability and confer robustness to genetic variants.
Article in eLife, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Current evidence on the relationships among five polymorphisms in the matrix metalloproteinases genes and prostate cancer risk.Scientific reports · 2024Pooled it
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- 5'untranslated regions provide a versatile toolkit for tunable exogenous protein expression.Molecular biology of the cell · 2026Article
- The association between methotrexate metabolism-related gene polymorphisms and therapeutic efficacy and toxicity in patients with rheumatoid arthritis.Arthritis research & therapy · 2026Article
- Effects of intraspecies and interspecies competition on genetic device construction and performance.mSphere · 2026Article
- A Regulator SNP Affecting the Transcription FactorHuman mutation · 2026Article
- Natural variation in regulatory code revealed through Bayesian analysis of plant pan-genomes and pan-transcriptomes.bioRxiv : the preprint server for biology · 2025Article
- Alternative transcription increases isoform complexity in Long Non-Coding RNAs and alters their functions in cancer.Non-coding RNA research · 2025Review
- Expression of SOX10, and micro-RNA 221 and Micro-RNA 222 in Oral Squamous Cell Carcinoma and Correlation with Clinicopathological Characteristics.Head and neck pathology · 2025Article
- Genome-wide rules of transcription factor cooperativity revealed throughbioRxiv : the preprint server for biology · 2025Article
- Stochastic gene expression in proliferating cells: Differing noise intensity in single-cell and population perspectives.PLoS computational biology · 2025Article
- Aberrant gene expression prediction across human tissues.Nature communications · 2025Article
- Global chromatin reorganization and regulation of genes with specific evolutionary ages during differentiation and cancer.Nucleic acids research · 2025Article
- Optimal solution to the set cover problem with a vicinity constraint for estimating genotype tissue expression profiles.Bioinformatics advances · 2025Article
- Global chromatin reorganization and regulation of genes with specific evolutionary ages during differentiation and cancer.bioRxiv : the preprint server for biology · 2024Article
- Stochastic Gene Expression in Proliferating Cells: Differing Noise Intensity in Single-Cell and Population Perspectives.bioRxiv : the preprint server for biology · 2024Article
- Exploration of the pearl millet phospholipase gene family to identify potential candidates for grain quality traits.BMC genomics · 2024Article
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genetic and environmental exposures cause variability in gene expression. Although most genes are affected in a population, their effect sizes vary greatly, indicating the existence of regulatory mechanisms that could amplify or attenuate expression variability. Here, we investigate the relationship between the sequence and transcription start site architectures of promoters and their expression variability across human individuals. We find that expression variability can be largely explained by a promoter's DNA sequence and its binding sites for specific transcription factors. We show that promoter expression variability reflects the biological process of a gene, demonstrating a selective trade-off between stability for metabolic genes and plasticity for responsive genes and those involved in signaling. Promoters with a rigid transcription start site architecture are more prone to have variable expression and to be associated with genetic variants with large effect sizes, while a flexible usage of transcription start sites within a promoter attenuates expression variability and limits genotypic effects. Our work provides insights into the variable nature of responsive genes and reveals a novel mechanism for supplying transcriptional and mutational robustness to essential genes through multiple transcription start site regions within a promoter.
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