Synthetic incoherent feedforward circuits show adaptation to the amount of their genetic template
Name
Bleris-2011-Synthetic incoherent feedforward circuits show adaptation to the amount of their genetic template.pdf
Size
1.49 MB
Format
Adobe PDF
Checksum (MD5)
43fa3ff37930a9e1b786497267db7f71
Author(s)
Bleris, Leonidas
Xie, Zhen
Glass, David
Adadey, Asa
Sontag, Eduardo
Benenson, Yaakov
Date Issued
August 2011
Journal
Molecular Systems Biology
Publisher
Nature Publishing Group
Citation
Bleris, Leonidas et al. “Synthetic Incoherent Feedforward Circuits Show Adaptation to the Amount of Their Genetic Template.” Molecular Systems Biology 7 (2011).
Version
Final published version
Abstract
Natural and synthetic biological networks must function reliably in the face of fluctuating stoichiometry of their molecular components. These fluctuations are caused in part by changes in relative expression efficiency and the DNA template amount of the network-coding genes. Gene product levels could potentially be decoupled from these changes via built-in adaptation mechanisms, thereby boosting network reliability. Here, we show that a mechanism based on an incoherent feedforward motif enables adaptive gene expression in mammalian cells. We modeled, synthesized, and tested transcriptional and post-transcriptional incoherent loops and found that in all cases the gene product adapts to changes in DNA template abundance. We also observed that the post-transcriptional form results in superior adaptation behavior, higher absolute expression levels, and lower intrinsic fluctuations. Our results support a previously hypothesized endogenous role in gene dosage compensation for such motifs and suggest that their incorporation in synthetic networks will improve their robustness and reliability.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported
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DOI of Published Version
https://doi.org/10.1038/msb.2011.49
