Combinatorial gene regulation by modulation of relative pulse timing

Area of Science:

• Cellular Biology
• Molecular Biology
• Systems Biology

Background:

• Transcription factors often activate in dynamic, stochastic pulses within individual cells.
• The role of dynamic pulse interactions in controlling gene expression remains unclear.

Purpose of the Study:

• To investigate if pulsatile transcription factors Msn2 and Mig1 use relative pulse timing for combinatorial gene regulation.
• To elucidate the mechanism of time-based gene regulation in Saccharomyces cerevisiae.

Main Methods:

• Quantitative single-cell time-lapse imaging in Saccharomyces cerevisiae.
• Analysis of Msn2 (activator) and Mig1 (repressor) pulse dynamics under varying inputs and constant conditions.
• Assessment of target gene expression based on the temporal overlap of Msn2 and Mig1 pulses.

Main Results:

• Msn2 and Mig1 exhibited pulsed activation with either overlapping or non-overlapping dynamics.
• Non-overlapping pulse dynamics of Msn2 and Mig1 were essential for efficient target gene activation.
• Glucose concentration modulated the temporal overlap of Msn2 and Mig1 pulses under constant conditions.

Conclusions:

• Relative pulse timing of transcription factors Msn2 and Mig1 is a key mechanism for combinatorial gene regulation.
• This study reveals a novel time-based mode of gene regulation in cellular systems.
• Temporal signal regulation, common in engineering and neurobiology, is suggested to be broadly functional in cellular signaling.