title: Spo0A~P imposes a temporal gate for the bimodal expression of competence in Bacillus subtilis.
abstract: ComK transcriptionally controls competence for the uptake of transforming DNA in Bacillus subtilis. Only 10%-20% of the cells in a clonal population are randomly selected for competence. Because ComK activates its own promoter, cells exceeding a threshold amount of ComK trigger a positive feedback loop, transitioning to the competence ON state. The transition rate increases to a maximum during the approach to stationary phase and then decreases, with most cells remaining OFF. The average basal rate of comK transcription increases transiently, defining a window of opportunity for transitions and accounting for the heterogeneity of competent populations. We show that as the concentration of the response regulator Spo0A∼P increases during the entry to stationary phase it first induces comK promoter activity and then represses it by direct binding. Spo0A∼P activates by antagonizing the repressor, Rok. This amplifies an inherent increase in basal level comK promoter activity that takes place during the approach to stationary phase and is a general feature of core promoters, serving to couple the probability of competence transitions to growth rate. Competence transitions are thus regulated by growth rate and temporally controlled by the complex mechanisms that govern the formation of Spo0A∼P. On the level of individual cells, the fate-determining noise for competence is intrinsic to the comK promoter. This overall mechanism has been stochastically simulated and shown to be plausible. Thus, a deterministic mechanism modulates an inherently stochastic process.
authors.affiliation: Public Health Research Institute Center of New Jersey Medical School, Newark, New Jersey, United States of America.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Mirouze
authors.forename: Yaanik
authors.initials: Y
authors.lastname: Desai
authors.forename: Arjun
authors.initials: A
authors.lastname: Raj
authors.forename: David
authors.initials: D
authors.lastname: Dubnau
mesh_terms: D001412:Bacillus subtilis; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D061269:DNA Transformation Competence / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D014169:Transformation, Bacterial; D054460:rho-Associated Kinases
chemical_list: D001426:Bacterial Proteins; C080950:Spo0A protein, Bacillus subtilis; D014157:Transcription Factors; C087449:comK protein, Bacillus subtilis; D054460:rho-Associated Kinases