Tunability and noise dependence in differentiation dynamics.
The dynamic process of differentiation depends on the architecture, quantitative parameters, and noise of underlying genetic circuits. However, it remains unclear how these elements combine to control cellular behavior. We analyzed the probabilistic and transient differentiation of Bacillus subtilis cells into the state of competence. A few key parameters independently tuned the frequency of initiation and the duration of competence episodes and allowed the circuit to access different dynamic regimes, including oscillation. Altering circuit architecture showed that the duration of competence events can be made more precise. We used an experimental method to reduce global cellular noise and showed that noise levels are correlated with frequency of differentiation events. Together, the data reveal a noise-dependent circuit that is remarkably resilient and tunable in terms of its dynamic behavior.
Süel
Gürol M
GM
Green Center Division for Systems Biology and Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Kulkarni
Rajan P
RP
Dworkin
Jonathan
J
Garcia-Ojalvo
Jordi
J
Elowitz
Michael B
MB
D001412:Bacillus subtilis / Q000166:cytology / Q000235:genetics* / Q000378:metabolism; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D005798:Genes, Bacterial; D007544:Isopropyl Thiogalactoside / Q000494:pharmacology; D008164:Luminescent Proteins / Q000096:biosynthesis; D008433:Mathematics; D008957:Models, Genetic; D015233:Models, Statistical; D009154:Mutation; D011336:Probability; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014169:Transformation, Bacterial
D001426:Bacterial Proteins; C093539:ComS protein, Bacillus subtilis; D008164:Luminescent Proteins; D014157:Transcription Factors; C054562:yellow fluorescent protein, Bacteria; C087449:comK protein, Bacillus subtilis; D007544:Isopropyl Thiogalactoside