During development, morphogens provide extracellular cues allowing cells to select a specific fate by inducing complex transcriptional programs. The mating pathway in budding yeast offers simplified settings to understand this process. Pheromone secreted by the mating partner triggers the activity of a MAPK pathway, which results in the expression of hundreds of genes. Using a dynamic expression reporter, we quantified the kinetics of gene expression in single cells upon exogenous pheromone stimulation and in the physiological context of mating. In both conditions, we observed striking differences in the timing of induction of mating‐responsive promoters. Biochemical analyses and generation of synthetic promoter variants demonstrated how the interplay between transcription factor binding and nucleosomes contributes to determine the kinetics of transcription in a simplified cell‐fate decision system.
During development, morphogens provide extracellular cues allowing cells to select a specific fate by inducing complex transcriptional programs. The mating pathway in budding yeast offers simplified settings to understand this process. Pheromone secreted by the mating partner triggers the activity of a MAPK pathway, which results in the expression of hundreds of genes. Using a dynamic expression reporter, we quantified the kinetics of gene expression in single cells upon exogenous pheromone stimulation and in the physiological context of mating. In both conditions, we observed striking differences in the timing of induction of mating-responsive promoters. Biochemical analyses and generation of synthetic promoter variants demonstrated how the interplay between transcription factor binding and nucleosomes contribute to determine the kinetics of transcription in a simplified cell-fate decision system. One Sentence Summary:Quantitative and dynamic single cell measurements in the yeast mating pathway uncover a complex temporal orchestration of gene expression events. Main TextCell-fate decisions play a key role in embryonic development. In order to make choices, cells integrate cues from neighboring cells as well as from morphogens. Signal transduction cascades relay this information inside the cell to translate these extra-cellular signals into defined biological responses. The cellular output includes the induction of complex transcriptional programs where specific genes are expressed to different levels and at various times (1, 2). Ultimately, these different expression programs will determine the fate of individual cells. The mating pathway in budding yeast has often been considered as a simplified cell-fate decision system, where each cell can either continue to cycle in the haploid state or decide to mate with a neighboring cell of opposing mating type. This decision results in an arrest of the cell cycle, formation of a mating projection and ultimately leads to the fusion with the partner to form a diploid zygote (3,4).Haploid budding yeast senses the presence of potential mating partners by detecting pheromone in the medium. This small peptide elicits the activation of a Mitogen-Activated Protein Kinase (MAPK) cascade (Sup Fig 1), which can integrate multiple cues such as stresses, cell cycle-stage or nutrient inputs (5-8). Once the MAPKs Fus3 and Kss1 are activated, they phosphorylate a large number of substrates and induce a new transcriptional program. Ste12 is the major transcription factor (TF) implicated in this response, and controls the induction of more than 200 genes (9).
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