Cell-to-cell variability in gene expression is regulated by casein kinase II
Casein kinase II Regulation of the Hot1 Transcription Factor Promotes Stochastic Gene Expression
Laura T. Burns and Susan R. Wente
Capsule
Background: Dynamic signaling events are required for cell-to-cell gene expression differences during responses to environmental stress.
Results: During hyperosmotic stress, casein kinase II (CK2) interacts with and phosphorylates the Hot1 transcription factor.
Conclusion: CK2 negatively regulates transcription activation to promote cell-to-cell variability in gene expression.
Significance: Multiple kinase inputs contribute to stochastic gene activity in response to environmental stress.
Abstract
In Saccharomyces cerevisiae, Hog1 MAPK is activated and induces a transcriptional program in response to hyperosmotic stress. Several Hog1-responsive genes exhibit stochastic transcription resulting in cell-to-cell variability in mRNA and protein levels. However, the mechanisms governing stochastic gene activity are not fully defined. Here we uncover a novel role for casein kinase II (CK2) in the cellular response to hyperosmotic stress. CK2 interacts with and phosphorylates the Hot1 transcription factor; however, Hot1 phosphorylation is not sufficient for controlling the stochastic response. The CK2 protein itself is required to negatively regulate mRNA expression of Hot1-responsive genes and Hot1 enrichment at target promoters. Single-cell gene expression analysis reveals altered activation of Hot1-targeted STL1 in ck2 mutants, resulting in a bimodal to unimodal shift in expression. Together, this work reveals a novel CK2 function during the hyperosmotic stress response that promotes cell-to-cell variability in gene expression.