title: Stochastic phenotype transition of a single cell in an intermediate region of gene state switching.
abstract: Multiple phenotypic states often arise in a single cell with different gene-expression states that undergo transcription regulation with positive feedback. Recent experiments show that, at least in E.coli, the gene state switching can be neither extremely slow nor exceedingly rapid as many previous theoretical treatments assumed. Rather, it is in the intermediate region which is difficult to handle mathematically. Under this condition, from a full chemical-master-equation description we derive a model in which the protein copy number, for a given gene state, follows a deterministic mean-field description while the protein-synthesis rates fluctuate due to stochastic gene state switching. The simplified kinetics yields a nonequilibrium landscape function, which, similar to the energy function for equilibrium fluctuation, provides the leading orders of fluctuations around each phenotypic state, as well as the transition rates between the two phenotypic states. This rate formula is analogous to Kramers' theory for chemical reactions. The resulting behaviors are significantly different from the two limiting cases studied previously.
authors.affiliation: Biodynamic Optical Imaging Center (BIOPIC), Peking University, Beijing 100871, People's Republic of China.|Beijing International Center for Mathematical Research (BICMR), Peking University, Beijing 100871, People's Republic of China.
authors.forename: Hao
authors.initials: H
authors.lastname: Ge
authors.affiliation: Department of Applied Mathematics, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Qian
authors.affiliation: Biodynamic Optical Imaging Center (BIOPIC), Peking University, Beijing 100871, People's Republic of China.|Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: X Sunney
authors.initials: XS
authors.lastname: Xie
mesh_terms: D004247:DNA / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics; D018628:Gene Dosage; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D008957:Models, Genetic; D010641:Phenotype; D059010:Single-Cell Analysis / Q000379:methods*; D013269:Stochastic Processes
chemical_list: D004247:DNA