Pulsatile Dynamics in the Yeast Proteome

Abstract

The activation of transcription factors in response to environmental conditions is fundamental to cellular regulation. Recent work has revealed that some transcription factors are activated in stochastic pulses of nuclear localization, rather than at a constant level, even in a constant environment. In such cases, signals control the mean activity of the transcription factor by modulating the frequency, duration, or amplitude of these pulses. Although specific pulsatile transcription factors have been identified in diverse cell types, it has remained unclear how prevalent pulsing is within the cell, how variable pulsing behaviors are between genes, and whether pulsing is specific to transcriptional regulators or employed more broadly. To address these issues, we performed a proteome-wide movie-based screen to systematically identify localization-based pulsing behaviors in Saccharomyces cerevisiae. The screen examined all genes in a previously developed fluorescent protein fusion library of 4159 strains in multiple media conditions. This approach revealed stochastic pulsing in 10 proteins, all transcription factors. In each case, pulse dynamics were heterogeneous and unsynchronized among cells in clonal populations. Pulsing is the only dynamic localization behavior we observed, and it tends to occur in pairs of paralagous and redundant proteins. Taken together, these results suggest that pulsatile dynamics play a pervasive role in yeast and may be similarly prevalent in other eukaryotic species.

p53 Pulses Diversify Target Gene Expression Dynamics in an mRNA Half-Life-Dependent Manner and Delineate Co-regulated Target Gene Subnetworks

“…As methods for quantifying intracellular signaling have improved, several signaling pathways have been found to transmit information using signals that pulse in time (Dalal et al, 2014; Levine et al, 2013). Pulsatile signaling has been found to serve diverse purposes in a biological context, including enforcing proportionality in gene expression (Cai et al, 2008), implementing timer processes (Levine et al, 2012), generating different gene expression or phosphorylation patterns (Ashall et al, 2009; Batchelor et al, 2009; Hansen and O’Shea, 2014; Hao and O’Shea, 2012; Nelson et al, 2004; Purvis et al, 2012; Tay et al, 2010; Toettcher et al, 2013), and improving signaling fidelity (Selimkhanov et al, 2014).…”

Mechanisms for the epigenetic inheritance of stress response in single cells

“…Transcription factors (TFs) are key components of the signaling cascades orchestrating a cell’s response to stress 8 . Curiously, many TFs exhibit dynamic behaviors in response to stress 9,10 . A recent genome-wide screen identified ~8% of the yeast TFs stochastically shuttle in and out of the nucleus under various conditions 9 .…”

“…Curiously, many TFs exhibit dynamic behaviors in response to stress 9,10 . A recent genome-wide screen identified ~8% of the yeast TFs stochastically shuttle in and out of the nucleus under various conditions 9 . Single-cell studies in recent years have revealed that transcription factors can transmit quantitative information corresponding to distinct environmental conditions 11,12 .…”

Determining the Limitations and Benefits of Noise in Gene Regulation and Signal Transduction through Single Cell, Microscopy-Based Analysis

“…This coordination of target gene expression would be difficult to achieve in an amplitude-modulated system where an increase in calcium leads to a proportional increase in nuclear Crz1 concentration, generating different ratios of target gene expression for each concentration of calcium (Figure 2B). A subsequent fluorescence microscopy-based screen by Dalal and colleagues showed that at least twelve different yeast transcription factors undergo similarly noisy short duration, frequency-modulated bursts of nuclear translocation [51]. These results suggest that such noisy transcription factor dynamics may be evolutionarily beneficial for a wide range of cellular responses.…”