Data for: Cooperative assembly confers regulatory specificity and long-term genetic circuit stability

A ubiquitous feature of eukaryotic transcriptional regulation is
cooperative self-assembly between transcription factors (TFs) and
DNA cis-regulatory motifs. It is thought that this strategy
enables specific regulatory connections to be formed in gene networks
between otherwise weakly-interacting, low-specificity molecular
components. Here, using synthetic gene circuits constructed in
yeast, we find that high regulatory specificity can emerge from
cooperative, multivalent interactions among artificial zinc finger-based
TFs. We show that circuits ‘wired’ using the strategy of
cooperative TF assembly are effectively insulated from aberrant
misregulation of the host cell genome. As we demonstrate
in experiments and mathematical models, this mechanism is
sufficient to rescue circuit-driven fitness defects, resulting in genetic
and functional stability of circuits in long-termcontinuous culture. Our
naturally-inspired approach offers a simple, generalizable
means for building high-fidelity, evolutionarily robust gene
circuits that can be scaled to a wide range of host organisms and
applications.