Promoter sequence and architecture determine expression variability and confer robustness to genetic variants.

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 involve

SUBMITTER: Einarsson H 

PROVIDER: S-EPMC9844987 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature