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DNA-Tethered RNA Polymerase for Programmable In vitro Transcription and Molecular Computation
Published on: December 29, 2021
Response acceleration in post-translationally regulated genetic circuits
Alexander Y Mitrophanov1, Eduardo A Groisman
1Department of Molecular Microbiology, Howard Hughes Medical Institute, Washington University School of Medicine, Campus Box 8230, 660 South Euclid Avenue, St Louis, MO 63110, USA.
Journal of Molecular Biology
|November 26, 2009
Summary
Chemical modifications like phosphorylation are crucial for transcription factors. This study reveals how "connector" proteins modulating these modifications impact gene expression dynamics in bacterial two-component systems.
Area of Science:
- Molecular Biology
- Systems Biology
- Biophysics
Background:
- Transcription factors require chemical modifications for function.
- Two-component systems (TCS) are key bacterial signal transduction pathways regulated by protein phosphorylation.
- Connectors modulate TCS phosphorylation in response to non-cognate signals, but their impact on system dynamics is unclear.
Purpose of the Study:
- To investigate how connector protein targeting mechanisms (sensor vs. regulator) affect TCS output dynamics.
- To determine the influence of these mechanisms on response acceleration, steady-state levels, and noise.
- To elucidate the relationship between genetic circuit architecture and dynamic properties.
Main Methods:
- Mathematical modeling of two-component systems with connector proteins.
- Analysis of different connector targeting strategies (sensor vs. regulator).
- Evaluation of response acceleration, steady-state output, and noise generation.
Main Results:
- Sensor-targeting connector mechanisms show significantly faster response acceleration compared to regulator-targeting mechanisms.
- Response acceleration differences are robust to kinetic parameter changes but depend on sensor-to-regulator ratios.
- Steady-state output levels and noise generation are largely independent of the connector targeting mechanism.
Conclusions:
- The architecture of genetic regulatory circuits, specifically connector targeting, critically influences the dynamic properties of two-component systems.
- Sensor-targeting by connectors enhances response speed, while steady-state output and noise are primarily determined by circuit parameters.
- Understanding these relationships is vital for predicting and engineering gene expression dynamics.
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