BROWSE

Related Researcher

Author's Photo

Ghim, Cheol-Min
Physical Biology & Biological Physics
Research Interests
  • Control of complex networks, Stochastic fluctuations in a cell, Biochemical information processing, Human microbiome, Ecological inference, Nonequilibrium active system

ITEM VIEW & DOWNLOAD

Genetic noise control via protein oligomerization

Cited 15 times inthomson ciCited 15 times inthomson ci
Title
Genetic noise control via protein oligomerization
Author
Ghim, Cheol-MinAlmaas, Eivind
Keywords
EXACT STOCHASTIC SIMULATION; ESCHERICHIA-COLI; BACTERIOPHAGE-LAMBDA; INTERACTION NETWORKS; FLUCTUATING ENVIRONMENTS; TRANSCRIPTION INITIATION; REGULATORY NETWORKS; RNA-POLYMERASE; TOGGLE SWITCH; BINDING
Issue Date
2008-11
Publisher
BIOMED CENTRAL LTD
Citation
BMC SYSTEMS BIOLOGY, v.2, no., pp.1 - 13
Abstract
Background: Gene expression in a cell entails random reaction events occurring over disparate time scales. Thus, molecular noise that often results in phenotypic and population-dynamic consequences sets a fundamental limit to biochemical signaling. While there have been numerous studies correlating the architecture of cellular reaction networks with noise tolerance, only a limited effort has been made to understand the dynamic role of protein-protein interactions. Results: We have developed a fully stochastic model for the positive feedback control of a single gene, as well as a pair of genes (toggle switch), integrating quantitative results from previous in vivo and in vitro studies. In particular, we explicitly account for the fast binding-unbinding kinetics among proteins, RNA polymerases, and the promoter/operator sequences of DNA. We find that the overall noise-level is reduced and the frequency content of the noise is dramatically shifted to the physiologically irrelevant high-frequency regime in the presence of protein dimerization. This is independent of the choice of monomer or dimer as transcription factor and persists throughout the multiple model topologies considered. For the toggle switch, we additionally find that the presence of a protein dimer, either homodimer or heterodimer, may significantly reduce its random switching rate. Hence, the dimer promotes the robust function of bistable switches by preventing the uninduced (induced) state from randomly being induced (uninduced). Conclusion: The specific binding between regulatory proteins provides a buffer that may prevent the propagation of fluctuations in genetic activity. The capacity of the buffer is a non-monotonic function of association-dissociation rates. Since the protein oligomerization per se does not require extra protein components to be expressed, it provides a basis for the rapid control of intrinsic or extrinsic noise. The stabilization of regulatory circuits and epigenetic memory in general is of direct implications to organism fitness. Our results also suggest possible avenues for the design of synthetic gene circuits with tunable robustness for a wide range of engineering purposes.
URI
Go to Link
DOI
10.1186/1752-0509-2-94
ISSN
1752-0509
Appears in Collections:
BME_Journal Papers
Files in This Item:
2-s2.0-56649114559.pdf Download

find_unist can give you direct access to the published full text of this article. (UNISTARs only)

Show full item record

qrcode

  • mendeley

    citeulike

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

MENU