Source 1primary paper2023Nucleic Acids Research
Toolkit/split transcriptional activator based gluconate switch
split transcriptional activator based gluconate switch
Taxonomy: Mechanism Branch / Architecture. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
The split transcriptional activator based gluconate switch is a multi-component mammalian gene-control system derived from the Escherichia coli gluconate-responsive regulator GntR. It uses gluconate-induced GntR dimerization to reconstitute a split transcriptional activator and activate transgene expression.
Usefulness & Problems
Why this is useful
This tool enables small-molecule control of transcription in mammalian cells using gluconate as the input signal. It is useful for building inducible transgene-expression systems based on a clinically licensed metabolite-responsive bacterial regulator.
Problem solved
It addresses the need for an inducible transcription switch that can couple the presence of gluconate to regulated gene expression in mammalian cells. The cited work specifically frames this as regulation of transgene expression by gluconate through rewired GntR-based control architectures.
Problem links
Need tighter control over gene expression timing or amplitude
DerivedThe split transcriptional activator based gluconate switch is a multi-component transcriptional control system built from the Escherichia coli gluconate-responsive regulator GntR. It uses gluconate-dependent GntR dimerization to activate gene expression through a split transcriptional activator in mammalian cells.
Taxonomy & Function
Primary hierarchy
Mechanism Branch
Architecture: A composed arrangement of multiple parts that instantiates one or more mechanisms.
Mechanisms
HeterodimerizationHeterodimerizationHeterodimerizationtranscriptional activation via split activator reconstitutionTechniques
No technique tags yet.
Target processes
transcriptionImplementation Constraints
cofactor dependency: cofactor requirement unknownencoding mode: genetically encodedimplementation constraint: context specific validationimplementation constraint: multi component delivery burdenoperating role: regulatorswitch architecture: multi componentswitch architecture: recruitmentswitch architecture: split
The design basis is the Escherichia coli gluconate-responsive transcriptional repressor GntR, adapted for use in mammalian cells. Practical construct details, promoter architecture, activation domains, linker composition, and delivery or expression conditions are not specified in the supplied evidence.
The supplied evidence does not provide quantitative performance data such as fold induction, background activity, dose response, kinetics, or cell-type breadth for the split activator configuration. Independent replication beyond the cited 2023 study is not provided in the evidence.
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Supporting Sources
Ranked Claims
Several switch designs were assembled based on the gluconate-responsive transcriptional repressor GntR from Escherichia coli.
Several switch designs were assembled based on the gluconate-responsive transcriptional repressor GntR from Escherichia coli.
Several switch designs were assembled based on the gluconate-responsive transcriptional repressor GntR from Escherichia coli.
Several switch designs were assembled based on the gluconate-responsive transcriptional repressor GntR from Escherichia coli.
Several switch designs were assembled based on the gluconate-responsive transcriptional repressor GntR from Escherichia coli.
Several switch designs were assembled based on the gluconate-responsive transcriptional repressor GntR from Escherichia coli.
Several switch designs were assembled based on the gluconate-responsive transcriptional repressor GntR from Escherichia coli.
Several switch designs were assembled based on the gluconate-responsive transcriptional repressor GntR from Escherichia coli.
Several switch designs were assembled based on the gluconate-responsive transcriptional repressor GntR from Escherichia coli.
Several switch designs were assembled based on the gluconate-responsive transcriptional repressor GntR from Escherichia coli.
Several switch designs were assembled based on the gluconate-responsive transcriptional repressor GntR from Escherichia coli.
Several switch designs were assembled based on the gluconate-responsive transcriptional repressor GntR from Escherichia coli.
Several switch designs were assembled based on the gluconate-responsive transcriptional repressor GntR from Escherichia coli.
Several switch designs were assembled based on the gluconate-responsive transcriptional repressor GntR from Escherichia coli.
Several switch designs were assembled based on the gluconate-responsive transcriptional repressor GntR from Escherichia coli.
Several switch designs were assembled based on the gluconate-responsive transcriptional repressor GntR from Escherichia coli.
Several switch designs were assembled based on the gluconate-responsive transcriptional repressor GntR from Escherichia coli.
Several switch designs were assembled based on the gluconate-responsive transcriptional repressor GntR from Escherichia coli.
Several switch designs were assembled based on the gluconate-responsive transcriptional repressor GntR from Escherichia coli.
Several switch designs were assembled based on the gluconate-responsive transcriptional repressor GntR from Escherichia coli.
A gluconate-responsive switch was built by using GntR dimerization in the presence of gluconate to activate gene expression from a split transcriptional activator.
Then, we utilized the ability of GntR to dimerize in the presence of gluconate to activate gene expression from a split transcriptional activator.
A gluconate-responsive switch was built by using GntR dimerization in the presence of gluconate to activate gene expression from a split transcriptional activator.
Then, we utilized the ability of GntR to dimerize in the presence of gluconate to activate gene expression from a split transcriptional activator.
A gluconate-responsive switch was built by using GntR dimerization in the presence of gluconate to activate gene expression from a split transcriptional activator.
Then, we utilized the ability of GntR to dimerize in the presence of gluconate to activate gene expression from a split transcriptional activator.
A gluconate-responsive switch was built by using GntR dimerization in the presence of gluconate to activate gene expression from a split transcriptional activator.
Then, we utilized the ability of GntR to dimerize in the presence of gluconate to activate gene expression from a split transcriptional activator.
A gluconate-responsive switch was built by using GntR dimerization in the presence of gluconate to activate gene expression from a split transcriptional activator.
Then, we utilized the ability of GntR to dimerize in the presence of gluconate to activate gene expression from a split transcriptional activator.
A gluconate-responsive switch was built by using GntR dimerization in the presence of gluconate to activate gene expression from a split transcriptional activator.
Then, we utilized the ability of GntR to dimerize in the presence of gluconate to activate gene expression from a split transcriptional activator.
A gluconate-responsive switch was built by using GntR dimerization in the presence of gluconate to activate gene expression from a split transcriptional activator.
Then, we utilized the ability of GntR to dimerize in the presence of gluconate to activate gene expression from a split transcriptional activator.
A gluconate-responsive switch was built by using GntR dimerization in the presence of gluconate to activate gene expression from a split transcriptional activator.
Then, we utilized the ability of GntR to dimerize in the presence of gluconate to activate gene expression from a split transcriptional activator.
A gluconate-responsive switch was built by using GntR dimerization in the presence of gluconate to activate gene expression from a split transcriptional activator.
Then, we utilized the ability of GntR to dimerize in the presence of gluconate to activate gene expression from a split transcriptional activator.
A gluconate-responsive switch was built by using GntR dimerization in the presence of gluconate to activate gene expression from a split transcriptional activator.
Then, we utilized the ability of GntR to dimerize in the presence of gluconate to activate gene expression from a split transcriptional activator.
A gluconate-responsive switch was built by using GntR dimerization in the presence of gluconate to activate gene expression from a split transcriptional activator.
Then, we utilized the ability of GntR to dimerize in the presence of gluconate to activate gene expression from a split transcriptional activator.
A gluconate-responsive switch was built by using GntR dimerization in the presence of gluconate to activate gene expression from a split transcriptional activator.
Then, we utilized the ability of GntR to dimerize in the presence of gluconate to activate gene expression from a split transcriptional activator.
A gluconate-responsive switch was built by using GntR dimerization in the presence of gluconate to activate gene expression from a split transcriptional activator.
Then, we utilized the ability of GntR to dimerize in the presence of gluconate to activate gene expression from a split transcriptional activator.
A gluconate-responsive switch was built by using GntR dimerization in the presence of gluconate to activate gene expression from a split transcriptional activator.
Then, we utilized the ability of GntR to dimerize in the presence of gluconate to activate gene expression from a split transcriptional activator.
A gluconate-responsive switch was built by using GntR dimerization in the presence of gluconate to activate gene expression from a split transcriptional activator.
Then, we utilized the ability of GntR to dimerize in the presence of gluconate to activate gene expression from a split transcriptional activator.
A gluconate-responsive switch was built by using GntR dimerization in the presence of gluconate to activate gene expression from a split transcriptional activator.
Then, we utilized the ability of GntR to dimerize in the presence of gluconate to activate gene expression from a split transcriptional activator.
A gluconate-responsive switch was built by using GntR dimerization in the presence of gluconate to activate gene expression from a split transcriptional activator.
Then, we utilized the ability of GntR to dimerize in the presence of gluconate to activate gene expression from a split transcriptional activator.
OFF- and ON-type switches were assembled by rewiring the native gluconate-dependent binding of GntR to target DNA sequences in mammalian cells.
Initially we assembled OFF- and ON-type switches by rewiring the native gluconate-dependent binding of GntR to target DNA sequences in mammalian cells.
OFF- and ON-type switches were assembled by rewiring the native gluconate-dependent binding of GntR to target DNA sequences in mammalian cells.
Initially we assembled OFF- and ON-type switches by rewiring the native gluconate-dependent binding of GntR to target DNA sequences in mammalian cells.
OFF- and ON-type switches were assembled by rewiring the native gluconate-dependent binding of GntR to target DNA sequences in mammalian cells.
Initially we assembled OFF- and ON-type switches by rewiring the native gluconate-dependent binding of GntR to target DNA sequences in mammalian cells.
OFF- and ON-type switches were assembled by rewiring the native gluconate-dependent binding of GntR to target DNA sequences in mammalian cells.
Initially we assembled OFF- and ON-type switches by rewiring the native gluconate-dependent binding of GntR to target DNA sequences in mammalian cells.
OFF- and ON-type switches were assembled by rewiring the native gluconate-dependent binding of GntR to target DNA sequences in mammalian cells.
Initially we assembled OFF- and ON-type switches by rewiring the native gluconate-dependent binding of GntR to target DNA sequences in mammalian cells.
OFF- and ON-type switches were assembled by rewiring the native gluconate-dependent binding of GntR to target DNA sequences in mammalian cells.
Initially we assembled OFF- and ON-type switches by rewiring the native gluconate-dependent binding of GntR to target DNA sequences in mammalian cells.
OFF- and ON-type switches were assembled by rewiring the native gluconate-dependent binding of GntR to target DNA sequences in mammalian cells.
Initially we assembled OFF- and ON-type switches by rewiring the native gluconate-dependent binding of GntR to target DNA sequences in mammalian cells.
OFF- and ON-type switches were assembled by rewiring the native gluconate-dependent binding of GntR to target DNA sequences in mammalian cells.
Initially we assembled OFF- and ON-type switches by rewiring the native gluconate-dependent binding of GntR to target DNA sequences in mammalian cells.
OFF- and ON-type switches were assembled by rewiring the native gluconate-dependent binding of GntR to target DNA sequences in mammalian cells.
Initially we assembled OFF- and ON-type switches by rewiring the native gluconate-dependent binding of GntR to target DNA sequences in mammalian cells.
OFF- and ON-type switches were assembled by rewiring the native gluconate-dependent binding of GntR to target DNA sequences in mammalian cells.
Initially we assembled OFF- and ON-type switches by rewiring the native gluconate-dependent binding of GntR to target DNA sequences in mammalian cells.
Random mutagenesis of GntR combined with phenotypic screening identified variants that significantly enhanced the functionality of the genetic devices.
By means of random mutagenesis of GntR combined with phenotypic screening, we identified variants that significantly enhanced the functionality of the genetic devices
Random mutagenesis of GntR combined with phenotypic screening identified variants that significantly enhanced the functionality of the genetic devices.
By means of random mutagenesis of GntR combined with phenotypic screening, we identified variants that significantly enhanced the functionality of the genetic devices
Random mutagenesis of GntR combined with phenotypic screening identified variants that significantly enhanced the functionality of the genetic devices.
By means of random mutagenesis of GntR combined with phenotypic screening, we identified variants that significantly enhanced the functionality of the genetic devices
Random mutagenesis of GntR combined with phenotypic screening identified variants that significantly enhanced the functionality of the genetic devices.
By means of random mutagenesis of GntR combined with phenotypic screening, we identified variants that significantly enhanced the functionality of the genetic devices
Random mutagenesis of GntR combined with phenotypic screening identified variants that significantly enhanced the functionality of the genetic devices.
By means of random mutagenesis of GntR combined with phenotypic screening, we identified variants that significantly enhanced the functionality of the genetic devices
Random mutagenesis of GntR combined with phenotypic screening identified variants that significantly enhanced the functionality of the genetic devices.
By means of random mutagenesis of GntR combined with phenotypic screening, we identified variants that significantly enhanced the functionality of the genetic devices
Random mutagenesis of GntR combined with phenotypic screening identified variants that significantly enhanced the functionality of the genetic devices.
By means of random mutagenesis of GntR combined with phenotypic screening, we identified variants that significantly enhanced the functionality of the genetic devices
Random mutagenesis of GntR combined with phenotypic screening identified variants that significantly enhanced the functionality of the genetic devices.
By means of random mutagenesis of GntR combined with phenotypic screening, we identified variants that significantly enhanced the functionality of the genetic devices
Random mutagenesis of GntR combined with phenotypic screening identified variants that significantly enhanced the functionality of the genetic devices.
By means of random mutagenesis of GntR combined with phenotypic screening, we identified variants that significantly enhanced the functionality of the genetic devices
Random mutagenesis of GntR combined with phenotypic screening identified variants that significantly enhanced the functionality of the genetic devices.
By means of random mutagenesis of GntR combined with phenotypic screening, we identified variants that significantly enhanced the functionality of the genetic devices
Approval Evidence
1 source1 linked approval claimfirst-pass slug split-transcriptional-activator-based-gluconate-switch
Then, we utilized the ability of GntR to dimerize in the presence of gluconate to activate gene expression from a split transcriptional activator.
Source:
mechanism designsupports
A gluconate-responsive switch was built by using GntR dimerization in the presence of gluconate to activate gene expression from a split transcriptional activator.
Then, we utilized the ability of GntR to dimerize in the presence of gluconate to activate gene expression from a split transcriptional activator.
Source:
Comparisons
Source-backed strengths
The system is mechanistically grounded in the gluconate-dependent dimerization behavior of GntR and was explicitly assembled to activate gene expression from a split transcriptional activator. The source literature also reports broader GntR-based OFF- and ON-type switch designs in mammalian cells, supporting the modularity of this regulator for transcriptional rewiring.
Source:
By means of random mutagenesis of GntR combined with phenotypic screening, we identified variants that significantly enhanced the functionality of the genetic devices
Compared with BcWCL1 PASΔ
split transcriptional activator based gluconate switch and BcWCL1 PASΔ address a similar problem space because they share transcription.
Shared frame: same top-level item type; shared target processes: transcription; shared mechanisms: heterodimerization
Compared with C120 promoter
split transcriptional activator based gluconate switch and C120 promoter address a similar problem space because they share transcription.
Shared frame: same top-level item type; shared target processes: transcription; shared mechanisms: heterodimerization
Strengths here: looks easier to implement in practice.
Compared with UVR8/UVR8
split transcriptional activator based gluconate switch and UVR8/UVR8 address a similar problem space because they share transcription.
Shared frame: same top-level item type; shared target processes: transcription; shared mechanisms: heterodimerization
Strengths here: looks easier to implement in practice.
Ranked Citations
- 1.