原创力文档delay-induced transient increase and heterogeneity in gene expression in negatively auto-regulated gene circuitsdelay-induced瞬态负自动调控基因的基因表达的增加和异质性电路.pdfVIP
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delay-induced transient increase and heterogeneity in gene expression in negatively auto-regulated gene circuitsdelay-induced瞬态负自动调控基因的基因表达的增加和异质性电路
Delay-Induced Transient Increase and Heterogeneity in
Gene Expression in Negatively Auto-Regulated Gene
Circuits
R. Maithreye, Ram Rup Sarkar, Veena K. Parnaik, Somdatta Sinha*
Centre for Cellular Molecular Biology (CSIR), Hyderabad, India
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.
Citation: Maithreye R, Sarkar RR, Parnaik VK, Sinha S (2008) Delay-Induced Transient Increase and Heterogeneity in Gene Expression in Negatively Auto-Regulated
Gene Circuits. PLoS ONE 3(8):
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