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Reconciling molecular regulatory mechanisms with noise patterns of bacterial metabolic promoters in induced and repressed states.

ABSTRACT: Assessing gene expression noise in order to obtain mechanistic insights requires accurate quantification of gene expression on many individual cells over a large dynamic range. We used a unique method based on 2-photon fluorescence fluctuation microscopy to measure directly, at the single cell level and with single-molecule sensitivity, the absolute concentration of fluorescent proteins produced from the two Bacillus subtilis promoters that control the switch between glycolysis and gluconeogenesis. We quantified cell-to-cell variations in GFP concentrations in reporter strains grown on glucose or malate, including very weakly transcribed genes under strong catabolite repression. Results revealed strong transcriptional bursting, particularly for the glycolytic promoter. Noise pattern parameters of the two antagonistic promoters controlling the nutrient switch were differentially affected on glycolytic and gluconeogenic carbon sources, discriminating between the different mechanisms that control their activity. Our stochastic model for the transcription events reproduced the observed noise patterns and identified the critical parameters responsible for the differences in expression profiles of the promoters. The model also resolved apparent contradictions between in vitro operator affinity and in vivo repressor activity at these promoters. Finally, our results demonstrate that negative feedback is not noise-reducing in the case of strong transcriptional bursting.

SUBMITTER: Ferguson ML

PROVIDER: S-EPMC3252923 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundCommunities with lower socioeconomic status and higher prevalence of racial/ethnic minority populations are often more exposed to environmental pollutants. Although studies have shown associations between aircraft noise and property values and various health outcomes, little is known about how aircraft noise exposures are sociodemographically patterned.ObjectiveOur aim was to describe characteristics of populations exposed to aviation noise by race/ethnicity, education, and income in the United States.MethodsAircraft noise contours characterized as day-night average sound level (DNL) were developed for 90 U.S. airports in 2010 for DNL ≥45 dB(A) in 1-dB(A) increments. We compared characteristics of exposed U.S. Census block groups at three thresholds (≥45, ≥55, and ≥65 dB(A)), assigned on the basis of the block group land area being ≥50% within the threshold, vs. unexposed block groups near study airports. Comparisons were made across block group race/ethnicity, education, and income categories within the study areas (n=4,031-74,253). We performed both multinomial and other various multivariable regression approaches, including models controlling for airport and models with random intercepts specifying within-airport effects and adjusting for airport-level means.ResultsAggregated across multiple airports, block groups with a higher Hispanic population had higher odds of being exposed to aircraft noise. For example, the multinomial analysis showed that a 10-percentage point increase in a block group's Hispanic population was associated with an increased odds ratio of 39% (95% CI: 25%, 54%) of being exposed to ≥65 dB(A) compared with block groups exposed to <45 dB(A). Block groups with higher proportions of residents with only a high school education had higher odds of being exposed to aircraft noise. Results were robust across multiple regression approaches; however, there was substantial heterogeneity across airports.DiscussionThese results suggest that across U.S. airports, there is indication of sociodemographic disparities in noise exposures. https://doi.org/10.1289/EHP9307.

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Reconciling molecular regulatory mechanisms with noise patterns of bacterial metabolic promoters in induced and repressed states.

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