Casein kinase II regulation of the Hot1 transcription factor promotes stochastic gene expression.

Burns LT, Wente SR
J Biol Chem. 2014 289 (25): 17668-79

PMID: 24817120 · PMCID: PMC4067201 · DOI:10.1074/jbc.M114.561217

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.

© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

MeSH Terms (11)

Casein Kinase II Gene Expression Regulation, Fungal Membrane Transport Proteins Mitogen-Activated Protein Kinases Mutation Osmotic Pressure Phosphorylation Saccharomyces cerevisiae Saccharomyces cerevisiae Proteins Stochastic Processes Transcription Factors

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