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HTH-domain-based dimerization-dependent mammalian gene switch framework

Candidate: toolkit itemType: multi component switch1 source documents6 linked claims
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Extracted Explainers

What the tool is doing

This framework uses HTH-domain-containing bacterial transcription factor parts and inducible protein-protein interactions to implement multi-input synthetic logic in mammalian cells. It shifts activation control toward dimerization-dependent assembly.

Source 1DOIPubMed

Resources required

The system requires HTH-domain-based transcription factor components and inducible dimerization partners assembled as fusion proteins in mammalian cells. It also requires appropriate gene-switch reporter architectures.

Source 1DOIPubMed

What problem it solves

It provides a way to build multi-input mammalian gene switches and logic gates from modular protein interactions. The abstract specifically says it enables OFF-type switches to be converted into more broadly applicable ON-type systems and allows responses to new inducers.

Source 1DOIPubMed

Alternatives

The abstract contrasts dimerization-dependent activation with DNA-binding-dependent activation. It also contrasts OFF-type and ON-type switch modes.

Source 1DOIPubMed

Evidence Snippets

Here we capitalize on the modular structure of these proteins to build a framework for multi-input logic gates relying on serial combinations of inducible protein-protein interactions. We found that for some TFs, their HTH domain alone is sufficient for DNA binding. By fusing the HTH domain to TFs, we established dimerization dependent rather than DNA-binding-dependent activation.
Evidence 1Source 1DOIPubMedprovenance

Supporting Sources

Linked Claims

Claim 1applicationsupports2023Source 1DOIPubMed

Combining OFF and ON modes of action produced a compact high-performance bandpass filter.

Quoted textsource-backed
By combining both OFF and ON modes of action, we built a compact, high-performance bandpass filter.
Claim 2applicationsupports2023Source 1DOIPubMed

Different combinations of pairwise fusion proteins afforded multiple 4-input 1-output AND and OR logic gate configurations.

Quoted textsource-backed
Combinations of different pairwise fusion proteins afforded a variety of 4-input 1-output AND and OR logic gate configurations.
Claim 3applicationsupports2023Source 1DOIPubMed

The dimerization-dependent framework enabled conversion of gene switches from OFF-type into ON-type systems and creation of mammalian gene switches responsive to new inducers.

Quoted textsource-backed
This enabled us to convert gene switches from OFF-type into more widely applicable ON-type systems and to create mammalian gene switches responsive to new inducers.
Claim 4applicationsupports2023Source 1DOIPubMed

The framework supported cytosolic and extracellular dimerization.

Quoted textsource-backed
Furthermore, we were able to show cytosolic and extracellular dimerization.
Claim 5engineering resultsupports2023Source 1DOIPubMed

Fusing the HTH domain to transcription factors established dimerization-dependent rather than DNA-binding-dependent activation.

Quoted textsource-backed
By fusing the HTH domain to TFs, we established dimerization dependent rather than DNA-binding-dependent activation.
Claim 6performancesupports2023Source 1DOIPubMed

Cascading up to five pairwise fusion proteins yielded robust multi-input AND logic gates.

Quoted textsource-backed
Cascading up to five pairwise fusion proteins yielded robust multi-input AND logic gates.