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Delay-Induced Transient Increase and Heterogeneity in Gene Expression in Negatively Auto-Regulated Gene Circuits

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  • R Maithreye
  • Ram Rup Sarkar
  • Veena K Parnaik
  • Somdatta Sinha

Abstract

A generic feature in all intracellular biochemical processes is the time required to complete the whole sequence of reactions to yield any observable quantity-from gene expression to circadian rhythms. This widespread phenomenon points towards the importance of time delay in biological functions. Theoretically time delay is known to be the source of instability, and has been attributed to lead to oscillations or transient dynamics in several biological functions. Negative feedback loops, common in biochemical pathways, have been shown to provide stability and withstand considerable variations and random perturbations of biochemical parameters. The interaction of these two opposing factors-of instability and homeostasis-are features that are widespread in intracellular processes. To test the effect of these divergent forces in the dynamics of gene expression, we have designed and constructed simple negatively auto-regulated gene circuits consisting of a basic regulator and transcriptional repressor module, and compared it with one, which has delayed repression. We show, both theoretically and experimentally, that delayed repression induces transient increase and heterogeneity in gene expression before the gain of stability effected by the negative feedback. This design, therefore, seems to be suitable for conferring both stability and variability in cells required for adaptive response to a noisy environment.

Suggested Citation

  • R Maithreye & Ram Rup Sarkar & Veena K Parnaik & Somdatta Sinha, 2008. "Delay-Induced Transient Increase and Heterogeneity in Gene Expression in Negatively Auto-Regulated Gene Circuits," PLOS ONE, Public Library of Science, vol. 3(8), pages 1-10, August.
    • Handle: RePEc:plo:pone00:0002972
    DOI: 10.1371/journal.pone.0002972
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    References listed on IDEAS

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    1. Alejandro Colman-Lerner & Andrew Gordon & Eduard Serra & Tina Chin & Orna Resnekov & Drew Endy & C. Gustavo Pesce & Roger Brent, 2005. "Regulated cell-to-cell variation in a cell-fate decision system," Nature, Nature, vol. 437(7059), pages 699-706, September.
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