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Mechanisms of transcriptional regulation underlying temporal integration of signals

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 <target> genes. Here we study how kinetic features of the IEG-<...

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Detalles Bibliográficos
Autores principales: Glauser, Dominique A., Schlegel, Werner
Formato: Texto
Lenguaje:English
Publicado: Oxford University Press 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1636431/
https://www.ncbi.nlm.nih.gov/pubmed/16998184
http://dx.doi.org/10.1093/nar/gkl654
Descripción
Sumario: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 <target> genes. Here we study how kinetic features of the IEG-<target> system allow temporal integration of stimuli in a pancreatic beta cell model of metabolic stimulation. Gene expression profiling revealed that beta cells produce drastically different transcriptional outputs in response to different stimuli durations. Noteworthy, most genes (87%) regulated by a sustained stimulation (4 h) were not regulated by a transient stimulation (1 h followed by 3 h without stimulus). We analyzed the induction kinetics of several previously identified IEGs and <targets>. IEG expression persisted as long as stimulation was maintained, but was rapidly lost upon stimuli removal, abolishing the delayed <target> induction. The molecular mechanisms coupling the duration of stimuli to quantitative <target> transcription were demonstrated for the AP-1 transcription factor. In conclusion, we propose that the network composed of IEGs and their <targets> dynamically functions to convert signal inputs of different durations into quantitative differences in global transcriptional adaptation. These findings provide a novel and more comprehensive view of dynamic gene regulation.