Molecular Time Sharing Through Dynamic Pulsing in Single Cells
Abstract
In cells, specific regulators often compete for limited amounts of a core enzymatic resource. It is typically assumed that competition leads to partitioning of core enzyme molecules among regulators at constant levels. Alternatively, however, different regulatory species could time share, or take turns utilizing, the core resource. Using quantitative time-lapse microscopy, we analyzed sigma factor activity dynamics, and their competition for RNA polymerase, in individual Bacillus subtilis cells under energy stress. Multiple alternative sigma factors were activated in approx. 1-hr pulses in stochastic and repetitive fashion. Pairwise analysis revealed that two sigma factors rarely pulse simultaneously and that some pairs are anti-correlated, indicating that RNAP utilization alternates among different sigma factors. Mathematical modeling revealed how stochastic time-sharing dynamics can emerge from pulse-generating sigma factor regulatory circuits actively competing for RNAP. Time sharing provides a mechanism for cells to dynamically control the distribution of cell states within a population. Since core molecular components are limiting in many other systems, time sharing may represent a general mode of regulation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 28, 2018
- Accession Number
- AD1079480
Entities
People
- James C. Locke
- Jin Park
- Jordi Garcia-Ojalvo
- Maria J. Hernandez-jimenez
- Marta Dies
- Michael Elowitz
- Sahand Hormoz
- Sofia Quinodoz
- Stephanie E. Smith-unna
- Yihan Lin
Organizations
- California Institute of Technology