BACK TO INDEX
Publications of Eduardo D. Sontag jointly with D. Glass
Articles in journal or book chapters
and Y. Benenson.
Synthetic incoherent feed-forward circuits show adaptation to the amount of their genetic template.
Molecular Systems Biology,
incoherent feedforward loop,
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 feed-forward 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.
BACK TO INDEX
This material is presented to ensure timely dissemination of
scholarly and technical work. Copyright and all rights therein
are retained by authors or by other copyright holders.
Last modified: Mon Nov 7 18:17:05 2022
This document was translated from BibTEX by