Stochastic transcriptional pulses orchestrate flagellum biosynthesis in <i>E. coli</i>

Kim, J. Mark; Garcia-Alcala, Mayra; Balleza, Enrique; Cluzel, Philippe

doi:10.1101/508580

Cited by 4 publications

(27 citation statements)

References 44 publications

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“…We first present a coarse-grained stochastic model for the regulation of class-2 genes by FlhDC. We then use the model to analyze and explain the steady-state distributions of class-2 activity and its dynamics observed in single-cell experiments [19]. Next, we propose possible molecular mechanisms underlying the main findings from our analysis and describe a filter-and-integrate mechanism for controlling noisy FlhDC signal in E. coli.…”

Section: Resultsmentioning

confidence: 91%

“…In the recent single-cell experiments [19], Kim et al used strains whose expression of class-1 genes was controlled by promoters of different strengths (see Sec. A in Supplemental Information (SI) for details of the experimental data).…”

Section: A a Stochastic Model For Class-1 And Class-2 Gene Expressiomentioning

confidence: 99%

“…1-2) with a few physiologically meaningful parameters and functions: two timescales τ 1 and τ 2 , a constant multiplicative noise strength ∆ 1 , a strain-dependent noise strength ∆ s (µ), and two response functions f s (C 1 ). By fitting all the single-cell data for different strains [19] with our model quantitatively, we determine the parameters and response functions, which help us identify the underlying mechanisms.…”

Section: A a Stochastic Model For Class-1 And Class-2 Gene Expressiomentioning

confidence: 99%

“…Recently, some of us (Kim et al [19]) measured gene expression dynamics of single E. coli cells over many generations by using a microfluidic device called the "mother machine" [20,21]. Surprisingly, the new single-cell data showed that flagellar promoters are stochastically activated in intermittent pulses, i.e., bursts of strong activity amid a quiet (near zero) background, rather than following a deterministic time-ordered program.…”

Section: Introductionmentioning

confidence: 99%

“…However, despite the ubiquity of the pulsatile expression pattern, the underlying molecular principles that govern the genesis and dynamics of pulses remain not fully understood. Here, using stochastic modeling constrained by the data from Kim et al [19], we wish to provide a theoretical framework with a minimal number of parameters to explain the origin of the observed stochastic dynamics of flagellar synthesis in E. coli.…”

Section: Introductionmentioning

confidence: 99%

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Filtering input fluctuations in intensity and in time underlies transcriptional pulses without feedback

Sassi¹,

Garcia-Alcala

Cluzel

et al. 2020

Preprint

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Bacterial flagellar synthesis is a complex process that requires coordinated expressions of three classes of genes. Recent single cell experiments in E. coli showed that flagellar class-2 promoters are activated in stochastic pulses instead of following a deterministic program as suggested by previous population measurements. Here, by using a stochastic model to quantitatively analyze these single-cell expression data, we identify two main factors that are responsible for the stochastic pulsating expression of class-2 genes. First, YdiV, an inhibitor of the master regulator Fl-hDC (a class-1 protein complex), creates a steep response function that filters out the small FlhDC fluctuations, and the filtered signal approximates a digital random telegraph signal. Second, the timescale (τ 2 ) governing the class-2 activity dynamics is longer than that of FlhDC fluctuations (τ 1 ), which indicates an integration effect wherein class-2 activity depends on previous FlhDC levels within a time-window τ 2 . Together, our results suggest that the noisy FlhDC input signal is first filtered with a threshold set by YdiV and then integrated over the long timescale τ 2 to yield the intermittent transcriptional pulses observed in E. coli flagellar synthesis. This filter-and-integrate strategy allows E. coli to avoid prematurely starting the expensive class-2 gene expression by small or large-but-short FlhDC fluctuations. Possible molecular mechanisms for the filter-and-integrate strategy are proposed. Our model is also used to make testable predictions on responses to realistic time-dependent stimuli. Finally, a comparison with a different gene regulation strategy enabled by an additional positive feedback loop in Salmonella is discussed.

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Section: Resultsmentioning

confidence: 91%

Section: A a Stochastic Model For Class-1 And Class-2 Gene Expressiomentioning

confidence: 99%

Section: A a Stochastic Model For Class-1 And Class-2 Gene Expressiomentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Filtering input fluctuations in intensity and in time underlies transcriptional pulses without feedback

Sassi¹,

Garcia-Alcala

Cluzel

et al. 2020

Preprint

Self Cite

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Design and validation of a dual-fluorescence reporter system to monitor bacterial gene expression in the gut environment

Moreira de Gouveia,

Reuter,

Garrivier

et al. 2023

Appl Microbiol Biotechnol

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HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

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Filtering input fluctuations in intensity and in time underlies stochastic transcriptional pulses without feedback

Sassi

Garcia-Alcala

Kim

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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Stochastic pulsatile dynamics have been observed in an increasing number of biological circuits with known mechanism involving feedback control and bistability. Surprisingly, recent single-cell experiments in Escherichia coli flagellar synthesis showed that flagellar genes are activated in stochastic pulses without the means of feedback. However, the mechanism for pulse generation in these feedbackless circuits has remained unclear. Here, by developing a system-level stochastic model constrained by a large set of single-cell E. coli flagellar synthesis data from different strains and mutants, we identify the general underlying design principles for generating stochastic transcriptional pulses without feedback. Our study shows that an inhibitor (YdiV) of the transcription factor (FlhDC) creates a monotonic ultrasensitive switch that serves as a digital filter to eliminate small-amplitude FlhDC fluctuations. Furthermore, we find that the high-frequency (fast) fluctuations of FlhDC are filtered out by integration over a timescale longer than the timescale of the input fluctuations. Together, our results reveal a filter-and-integrate design for generating stochastic pulses without feedback. This filter-and-integrate mechanism enables a general strategy for cells to avoid premature activation of the expensive downstream gene expression by filtering input fluctuations in both intensity and time so that the system only responds to input signals that are both strong and persistent.

show abstract

Stochastic transcriptional pulses orchestrate flagellum biosynthesis in E. coli

Cited by 4 publications

References 44 publications

Filtering input fluctuations in intensity and in time underlies transcriptional pulses without feedback

Filtering input fluctuations in intensity and in time underlies transcriptional pulses without feedback

Design and validation of a dual-fluorescence reporter system to monitor bacterial gene expression in the gut environment

Filtering input fluctuations in intensity and in time underlies stochastic transcriptional pulses without feedback

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