ArticleScientific reports2016
Improvement of the reverse tetracycline transactivator by single amino acid substitutions that reduce leaky target gene expression to undetectable levels.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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48 citing papers in PubMed, 78 citations in OpenAlex.
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- Mechanisms of and mitigating strategies for cellular immune responses to CRISPR-associated nucleases in genome editing therapy.Frontiers in medicine · 2026Review
- A peptide display system identifies a potent mutant β-melanocyte-stimulating hormone agonist of melanocortin-4 receptor.Cell genomics · 2025Article
- Protocol for inducible expression of small non-coding RNAs using a tet-on system in Saccharomyces cerevisiae.STAR protocols · 2025Article
- Development of compact transcriptional effectors using high-throughput measurements in diverse contexts.Nature biotechnology · 2025Article
- Transcriptional regulation as a dose-dependent process: insights from transcription factor tuning.Open biology · 2025Review
- Free introns of tRNAs as complementarity-dependent regulators of gene expression.Molecular cell · 2025Article
- Targeted UDP-glucose ceramide glucosyltransferase stable overexpression induces a metabolic switch improving cell performance at high cell density.Frontiers in bioengineering and biotechnology · 2025Article
- Inducible cell lines producing replication-defective human immunodeficiency virus particles containing envelope glycoproteins stabilized in a pretriggered conformation.Journal of virology · 2024Article
- Possible roles of CAHS proteins from Tardigrade in osmotic stress tolerance in mammalian cells.Cell structure and function · 2024Article
- Tracing Quiescent Cancer Cells In Vivo.Cancers · 2024Review
- A Standardized Set of MoClo-Compatible Inducible Promoter Systems for Tunable Gene Expression in Yeast.ACS synthetic biology · 2024Article
- Single-cell chromatin state transitions during epigenetic memory formation.bioRxiv : the preprint server for biology · 2023Article
- Engineering activatable promoters for scalable and multi-input CRISPRa/i circuits.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Drug-Inducible Gene Therapy Effectively Reduces Spontaneous Seizures in Kindled Rats but Creates Off-Target Side Effects in Inhibitory Neurons.International journal of molecular sciences · 2023Article
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
Conditional gene expression systems that enable inducible and reversible transcriptional control are essential research tools and have broad applications in biomedicine and biotechnology. The reverse tetracycline transcriptional activator is a canonical system for engineered gene expression control that enables graded and gratuitous modulation of target gene transcription in eukaryotes from yeast to human cell lines and transgenic animals. However, the system has a tendency to activate transcription even in the absence of tetracycline and this leaky target gene expression impedes its use. Here, we identify single amino-acid substitutions that greatly enhance the dynamic range of the system in yeast by reducing leaky transcription to undetectable levels while retaining high expression capacity in the presence of inducer. While the mutations increase the inducer concentration required for full induction, additional sensitivity-enhancing mutations can compensate for this effect and confer a high degree of robustness to the system. The novel transactivator variants will be useful in applications where tight and tunable regulation of gene expression is paramount.
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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.