Space-induced bifurcation in repression-based transcriptional circuits.
BACKGROUND
Albeit the molecular mechanisms of gene expression are well documented, our understanding of their dynamics is much less advanced. Recent experimental evidence has revealed that gene expression might be accurately organized in space, with several molecular actors localized to specific positions in the cell. However, the influence of this spatial localization on the dynamics of gene expression is unclear. This issue is also central in synthetic biology, where one usually considers the spatial localization in the cell of the genes of the inserted synthetic construct as irrelevant for its temporal dynamics.


RESULTS
Here, we assessed the influence of the spatial distribution of the genes on the dynamics of 3-gene transcriptional ring networks regulated by repression, i.e. repressilator circuits, using individual-based modelling to simulate their dynamics in two and three space dimensions. Our simulations suggest that variations of spatial parameters - namely the degree of demixing of the positions of the gene or the spatial range of the mRNA and proteins (i.e. the typical distance they travel before degradation) - have dramatic effects by switching the dynamical regime from spontaneous oscillations to a stationary state where each species fluctuates around a constant value. By analogy with the bifurcations arising from the variation of kinetic parameters, we referred to those transitions as space-induced bifurcations.


CONCLUSIONS
Taken together, our results strongly support the idea that the spatial organization of the molecular actors of transcriptional networks is crucial for the dynamics of gene expression and suggest that the spatial localization of the synthetic genes in the cell could be used as an additional toggle to control the dynamics of the inserted construct in synthetic biology experiments.
INRIA, 56 Blvd Niels Bohr, Villeurbanne, 69603, France. amanda.lo-van@insa-lyon.fr.|LIRIS, Université de Lyon, UMR 5205 CNRS-INSA, Villeurbanne, 69621, France. amanda.lo-van@insa-lyon.fr.
Amanda Lo
AL
Van
INRIA, 56 Blvd Niels Bohr, Villeurbanne, 69603, France. hedi.soula@insa-lyon.fr.|Université de Lyon, Inserm UMR1060, Villeurbanne, 69621, France. hedi.soula@insa-lyon.fr.
Hedi A
HA
Soula
INRIA, 56 Blvd Niels Bohr, Villeurbanne, 69603, France. hugues.berry@inria.fr.|LIRIS, Université de Lyon, UMR 5205 CNRS-INSA, Villeurbanne, 69621, France. hugues.berry@inria.fr.
Hugues
H
Berry
D003198:Computer Simulation; D005786:Gene Expression Regulation / Q000502:physiology*; D053263:Gene Regulatory Networks / Q000235:genetics / Q000502:physiology*; D008957:Models, Genetic; D062206:Spatial Analysis; D013045:Species Specificity; D058615:Synthetic Biology / Q000379:methods*