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Author Spotlight: An Integrated Workflow to Study the Promoter-Centric Spatio-Temporal Genome Architecture in Scarce Cell Populations
Published on: April 21, 2023
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Promoter sequence and architecture determine expression variability and confer robustness to genetic variants
Hjörleifur Einarsson1, Marco Salvatore1, Christian Vaagensø1
1Department of Biology, University of Copenhagen, Copenhagen, Denmark.
Elife
|November 15, 2022
Summary
Gene expression variability is influenced by promoter DNA sequence and transcription start site architecture. This impacts gene function, balancing stability for essential genes with plasticity for responsive ones.
Area of Science:
- Genomics
- Molecular Biology
- Systems Biology
Background:
- Genetic and environmental factors drive variations in gene expression across individuals.
- Understanding the regulatory mechanisms behind expression variability is crucial for deciphering gene function and biological responses.
Purpose of the Study:
- To investigate the link between promoter sequence/architecture and gene expression variability in humans.
- To explore how promoter characteristics influence the stability and plasticity of gene expression.
Main Methods:
- Analysis of promoter DNA sequences and transcription start site (TSS) architectures.
- Correlation of promoter features with gene expression variability data across human populations.
- Examination of the relationship between expression variability and gene biological processes.
Main Results:
- Promoter DNA sequence and transcription factor binding sites significantly explain gene expression variability.
- Expression variability correlates with gene function: metabolic genes show stability, while signaling and responsive genes exhibit plasticity.
- Rigid TSS architecture is linked to higher expression variability and larger genetic variant effects; flexible TSS usage attenuates variability.
Conclusions:
- Promoter architecture and sequence are key determinants of gene expression variability.
- A trade-off exists between expression stability (essential genes) and plasticity (responsive genes).
- Multiple TSS regions offer a mechanism for transcriptional and mutational robustness in essential genes.
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