title: Casein kinase II regulation of the Hot1 transcription factor promotes stochastic gene expression.
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.
authors.affiliation: From the Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
authors.forename: Laura T
authors.initials: LT
authors.lastname: Burns
authors.affiliation: From the Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 susan.wente@vanderbilt.edu.
authors.forename: Susan R
authors.initials: SR
authors.lastname: Wente
mesh_terms: D047390:Casein Kinase II / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal / Q000502:physiology*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009997:Osmotic Pressure / Q000502:physiology; D010766:Phosphorylation / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013269:Stochastic Processes; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: C120535:HOT1 protein, S cerevisiae; D026901:Membrane Transport Proteins; C470555:STL1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D047390:Casein Kinase II; C088589:HOG1 protein, S cerevisiae; D020928:Mitogen-Activated Protein Kinases
keywords: Gene Expression; Mitogen-activated Protein Kinase (MAPK); Protein Phosphorylation; Stress Response; Transcription Factor