Nucleic Acids Research Advance Access published online on September 22, 2006
Nucleic Acids Research, doi:10.1093/nar/gkl654
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2006 The Author(s).
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Molecular Biology |
Mechanisms of transcriptional regulation underlying temporal integration of signals
Fondation pour Recherches Médicales, University of Geneva Switzerland
*To whom correspondence should be addressed at Fondation pour Recherches Médicales, Avenue de la Roseraie 64, 1211 Geneva, Switzerland. Tel: +41 22 382 38 11; Fax: +41 22 347 59 79; Email: werner.schlegel{at}medecine.unige.ch
Received August 22, 2006. Revised August 22, 2006. Accepted August 25, 2006.
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.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Legewie, D. Dienst, A. Wilde, H. Herzel, and I. M. Axmann Small RNAs Establish Delays and Temporal Thresholds in Gene Expression Biophys. J., October 1, 2008; 95(7): 3232 - 3238. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Glauser and W. Schlegel Sequential actions of ERK1/2 on the AP-1 transcription factor allow temporal integration of metabolic signals in pancreatic {beta} cells FASEB J, October 1, 2007; 21(12): 3240 - 3249. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A Glauser and W. Schlegel The emerging role of FOXO transcription factors in pancreatic {beta} cells J. Endocrinol., May 1, 2007; 193(2): 195 - 207. [Abstract] [Full Text] [PDF]
|
|