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Abduction and asylum in the lives of transcription factors.

ABSTRACT: Recent studies suggest that there are many nonfunctional transcription factor binding sites along a genome. Although these "decoy" sites compete with the promoter region for binding of transcription factors, they may also protect these proteins from degradation. We show that in the limit of perfect protection, where bound transcription factors are never degraded, the competitive effect of nonfunctional binding sites is completely canceled out by the stability gained from reduced degradation. We examine the response of an autoregulated gene to the total number of transcription factors to quantify the consequences of competition for transcription factors. We show that intuition about this system can be gained by mathematically constructing a single gene with effective parameters that reproduce the behavior of a gene with added decoy sites. In analogy to dressed particles in many-body systems we term this description a "quasi gene." We find that protective decoys buffer against noise by reducing correlations between transcription factors, specifically in the case of production of transcription factors in bursts. We show that the addition of protective decoy sites causes the level of gene expression to approach that predicted from deterministic mass action models. Finally, we show that protective decoy sites decrease the size of the region of parameter space that exhibits bistability.

SUBMITTER: Burger A

PROVIDER: S-EPMC2840107 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature

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Abduction and asylum in the lives of transcription factors.

Burger Anat A Walczak Aleksandra M AM Wolynes Peter G PG

Proceedings of the National Academy of Sciences of the United States of America 20100216 9

Recent studies suggest that there are many nonfunctional transcription factor binding sites along a genome. Although these "decoy" sites compete with the promoter region for binding of transcription factors, they may also protect these proteins from degradation. We show that in the limit of perfect protection, where bound transcription factors are never degraded, the competitive effect of nonfunctional binding sites is completely canceled out by the stability gained from reduced degradation. We ...[more]

PMID: 20160109

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Project description:BackgroundUnderstanding the factors influencing SARS-CoV-2 transmission in asylum seekers and refugees living in centres is crucial to determine targeted public health policies protecting these populations fairly and efficiently. In response, this study was designed to explore the pandemic's spread into asylum centres during the first wave of the pandemic in Switzerland. Specifically, it aimed to identify the risk factors associated with a positive anti-SARS-CoV-2 seroprevalence test after the first semi-confinement period (16 March to 27 April 2020) amongst asylum seekers and refugees living in centres.MethodsThis research is part of SérocoVID, a seroepidemiologic study of SARS-CoV-2 infection conducted in the canton of Vaud, Switzerland. Migrants living in two asylum centres, one known to have had an epidemic outbreak, were invited to participate in this study. Anti-SARS-CoV-2 IgG and IgA antibodies targeting the spike viral protein were measured in all participants using a Luminex immunoassay. Each participant also completed a questionnaire measuring socio-demographic characteristics, medical history (comorbidities, smoking status, BMI, flu-like symptoms), health literacy, public health recommendations (wearing a masque in a public area, social distancing and hands cleaning), behaviours and exposures (daily life activities, number of contacts weekly). The association of these independent variables with the serologic test result were estimated using a multivariable logistic regression model.FindingsA total of 124 participants from the two asylum centres took part in the study (Centre 1, n = 82; Centre 2, n = 42). The mean participation rate was 36.7%. The seroprevalence in Centres 1 and 2 were 13% [95% CI 0.03, 0.14] and 50% [0.34, 0.65], respectively. Next, 40.63% of SARS-CoV-2 positive people never developed symptoms (asymptomatic cases), and no one had severe forms of the Covid-19 disease requiring hospitalisation. Participants report high compliance with public health measures, especially hygiene rules (96.3% of positive answers) and social distancing (88.7%). However, only 11.3% said they always wore a masque in public. After adjusting for individual characteristics, infection risk was lower amongst people with high health literacy (aOR 0.16, p = 0.007 [0.04, 0.60]) and smokers (aOR 0.20, p = 0.013 [0.06, 0.69]).ConclusionDespite the lack of severe complications of Covid-19 disease in this study, findings suggest that developing targeted public health measures, especially for the low health literacy population, would be necessary to limit the risk of outbreaks in asylum centres and improve this population's safety. Further investigations and qualitative approach are required to understand more finely how living conditions, risks and behaviours such as tobacco consumption, and the adoption of protective measures impact SARS-CoV-2 infection.

Project description:Dinoflagellates possess many physiological processes that appear to be under post-transcriptional control. However, the extent to which their genes are regulated post-transcriptionally remains unresolved. To gain insight into the roles of differential mRNA stability and de novo transcription in dinoflagellates, we biosynthetically labeled RNA with 4-thiouracil to isolate newly transcribed and pre-existing RNA pools in Karenia brevis. These isolated fractions were then used for analysis of global mRNA stability and de novo transcription by hybridization to a K. brevis microarray. Global K. brevis mRNA half-lives were calculated from the ratio of newly transcribed to pre-existing RNA for 7086 array features using the online software HALO (Half-life Organizer). Overall, mRNA half-lives were substantially longer than reported in other organisms studied at the global level, ranging from 42 minutes to greater than 144 h, with a median of 33 hours. Consistent with well-documented trends observed in other organisms, housekeeping processes, including energy metabolism and transport, were significantly enriched in the most highly stable messages. Shorter-lived transcripts included a higher proportion of transcriptional regulation, stress response, and other response/regulatory processes. One such family of proteins involved in post-transcriptional regulation in chloroplasts and mitochondria, the pentatricopeptide repeat (PPR) proteins, had dramatically shorter half-lives when compared to the arrayed transcriptome. As transcript abundances for PPR proteins were previously observed to rapidly increase in response to nutrient addition, we queried the newly synthesized RNA pools at 1 and 4 h following nitrate addition to N-depleted cultures. Transcriptome-wide there was little evidence of increases in the rate of de novo transcription during the first 4 h, relative to that in N-depleted cells, and no evidence for increased PPR protein transcription. These results lend support to the growing consensus of post-transcriptional control of gene expression in dinoflagellates.

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Abduction and asylum in the lives of transcription factors.

Publications

Abduction and asylum in the lives of transcription factors.

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