ArticleNucleic acids research2013
Synthetic mammalian trigger-controlled bipartite transcription factors.
Article in Nucleic acids research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 30 citations in OpenAlex.
- Article
- An electrogenetic interface to program mammalian gene expression by direct current.Nature metabolism · 2023Article
- Combinatorial protein dimerization enables precise multi-input synthetic computations.Nature chemical biology · 2023Article
- Control of Multigene Expression Stoichiometry in Mammalian Cells Using Synthetic Promoters.ACS synthetic biology · 2021Article
- Rewiring of endogenous signaling pathways to genomic targets for therapeutic cell reprogramming.Nature communications · 2020Article
- Designing cell function: assembly of synthetic gene circuits for cell biology applications.Nature reviews. Molecular cell biology · 2018Review
- Design principles for nuclease-deficient CRISPR-based transcriptional regulators.FEMS yeast research · 2018Review
- Self-adjusting synthetic gene circuit for correcting insulin resistance.Nature biomedical engineering · 2017Article
- Engineering prokaryotic transcriptional activators as metabolite biosensors in yeast.Nature chemical biology · 2016Article
- Synthetic dual-input mammalian genetic circuits enable tunable and stringent transcription control by chemical and light.Nucleic acids research · 2016Article
- Mammalian synthetic biology: emerging medical applications.Journal of the Royal Society, Interface · 2015Review
- Systematic transfer of prokaryotic sensors and circuits to mammalian cells.ACS synthetic biology · 2014Article
- Rule-based design of synthetic transcription factors in eukaryotes.ACS synthetic biology · 2014Article
- Antagonistic control of a dual-input mammalian gene switch by food additives.Nucleic acids research · 2014Article
- Uncoupling of the dynamics of host-pathogen interaction uncovers new mechanisms of viral interferon antagonism at the single-cell level.Nucleic acids research · 2014Article
- Optogenerapy: When bio-electronic implant enters the modern syringe era.Porto biomedical journalArticle
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Synthetic biology has significantly advanced the design of synthetic control devices, gene circuits and networks that can reprogram mammalian cells in a trigger-inducible manner. Prokaryotic helix-turn-helix motifs have become the standard resource to design synthetic mammalian transcription factors that tune chimeric promoters in a small molecule-responsive manner. We have identified a family of Actinomycetes transcriptional repressor proteins showing a tandem TetR-family signature and have used a synthetic biology-inspired approach to reveal the potential control dynamics of these bi-partite regulators. Daisy-chain assembly of well-characterized prokaryotic repressor proteins such as TetR, ScbR, TtgR or VanR and fusion to either the Herpes simplex transactivation domain VP16 or the Krueppel-associated box domain (KRAB) of the human kox-1 gene resulted in synthetic bi- and even tri-partite mammalian transcription factors that could reversibly program their individual chimeric or hybrid promoters for trigger-adjustable transgene expression using tetracycline (TET), γ-butyrolactones, phloretin and vanillic acid. Detailed characterization of the bi-partite ScbR-TetR-VP16 (ST-TA) transcription factor revealed independent control of TET- and γ-butyrolactone-responsive promoters at high and double-pole double-throw (DPDT) relay switch qualities at low intracellular concentrations. Similar to electromagnetically operated mechanical DPDT relay switches that control two electric circuits by a fully isolated low-power signal, TET programs ST-TA to progressively switch from TetR-specific promoter-driven expression of transgene one to ScbR-specific promoter-driven transcription of transgene two while ST-TA flips back to exclusive transgene 1 expression in the absence of the trigger antibiotic. We suggest that natural repressors and activators with tandem TetR-family signatures may also provide independent as well as DPDT-mediated control of two sets of transgenes in bacteria, and that their synthetic transcription-factor analogs may enable the design of compact therapeutic gene circuits for gene and cell-based therapies.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.