Two-component genetic switch as a synthetic module with tunable stability.
Despite stochastic fluctuations, some genetic switches are able to retain their expression states through multiple cell divisions, providing epigenetic memory. We propose a novel rationale for tuning the functional stability of a simple synthetic gene switch through protein dimerization. Introducing an approximation scheme to access long-time stochastic dynamics of multiple-component gene circuits, we find that the spontaneous switching rate may exhibit greater than 8 orders of magnitude variation. The manipulation of the circuit's biochemical properties offers a practical strategy for designing robust epigenetic memory with synthetic circuits.
Ghim
C-M
CM
Biosciences & Biotechnology Division, Lawrence Livermore National Laboratory, Livermore, California 94550, USA.
Almaas
E
E
D004247:DNA / Q000235:genetics* / Q000378:metabolism; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D019281:Dimerization; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D007700:Kinetics; D008957:Models, Genetic; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D013269:Stochastic Processes
D012097:Repressor Proteins; D004247:DNA; D012321:DNA-Directed RNA Polymerases