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Mentions: Establishment of a new expression steady state upon sustained stimulation suggests that IEG induction is not solely a response to a sudden metabolic change, but rather that the levels of IEG expression are continuously adjusted according to metabolic status of the cell. We wondered whether this effect would occur on a longer time scale and whether this system will also sense subtle variations in the intensity of a metabolic stimulation. Thus, we determined the expression levels of two IEGs (c-fos and sgk1) after long-term culture (20 h) at various glucose concentrations (from 1 to 25 mM, but without co-stimulant). The results in Figure 4 show that the expression levels of both IEGs are gradually adjusted with increasing glucose levels. Notably, maximal variations occur within a physiological range of glucose concentrations between 5 and 10 mM. With these mild stimulations (as cpt-cAMP co-stimulant was not used), mRNA levels for the moderately-responding b3gt2 gene were not significantly affected (data not shown). However, after 20 h of co-stimulation with high glucose plus cpt-cAMP, we observed mRNA levels for b3gt2 and c-fos that were similar to those observed at 6 h (Figure 3 and data not shown).
Mechanisms of transcriptional regulation underlying temporal integration of signals
Bottom Line: IEG expression persisted as long as stimulation was maintained, but was rapidly lost upon stimuli removal, abolishing the delayed
Affiliation: Fondation pour Recherches Médicales, University of Geneva, Switzerland.
Abstract: How cells convert the duration of signals into differential adaptation of gene expression is a poorly understood issue. Signal-induced immediate-early gene (IEG) expression couples early signals to late expression of downstream
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