Molecular time sharing through dynamic pulsing in single cells

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 tu...

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Detalles Bibliográficos
Autores: Park, Jin, Dies, Marta, Lin, Yihan, Hormoz, Sahand, Smith-Unna, Stephanie E., Quinodoz, Sofia, Hernández Jiménez, María Jesús, García Ojalvo, Jordi, Locke, James C.W., Elowitz, Michael B.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/34134
Acceso en línea:http://hdl.handle.net/10230/34134
http://dx.doi.org/10.1016/j.cels.2018.01.011
Access Level:acceso abierto
Palabra clave:Microfluidics
Partitioning
Pulsing
Shared resources
Time sharing
Descripción
Sumario: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 ∼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.