ArticleNucleic acids research2016
Locked and proteolysis-based transcription activator-like effector (TALE) regulation.
Article in Nucleic acids research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Artificial repression looping control by regulated autoinhibition of transcription activator-like effector dimer proteins.Nucleic acids research · 2026Article
- Conditional Split Inteins: Adaptable Tools for Programming Protein Functions.International journal of molecular sciences · 2025Review
- A synthetic population-level oscillator in non-microfluidic environments.Communications biology · 2023Article
- Small-molecule inducible transcriptional control in mammalian cells.Critical reviews in biotechnology · 2020Review
- Engineering and Rewiring of a Calcium-Dependent Signaling Pathway.ACS synthetic biology · 2020Article
- Tuning up Transcription Factors for Therapy.Molecules (Basel, Switzerland) · 2020Review
- An expanded library of orthogonal split inteins enables modular multi-peptide assemblies.Nature communications · 2020Article
- Split-TALE: A TALE-Based Two-Component System for Synthetic Biology Applications in Planta.Plant physiology · 2019Article
- Polarized displacement by transcription activator-like effectors for regulatory circuits.Nature chemical biology · 2019Article
- Conditional replication of oncolytic viruses based on detection of oncogenic mRNA.Gene therapy · 2018Review
- Genome-Editing Technologies: Principles and Applications.Cold Spring Harbor perspectives in biology · 2016Review
- Post-translational control of genetic circuits using Potyvirus proteases.Nucleic acids research · 2016Article
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Development of orthogonal, designable and adjustable transcriptional regulators is an important goal of synthetic biology. Their activity has been typically modulated through stimulus-induced oligomerization or interaction between the DNA-binding and activation/repression domain. We exploited a feature of the designable Transcription activator-like effector (TALE) DNA-binding domain that it winds around the DNA which allows to topologically prevent it from binding by intramolecular cyclization. This new approach was investigated through noncovalent ligand-induced cyclization or through a covalent split intein cyclization strategy, where the topological inhibition of DNA binding by cyclization and its restoration by a proteolytic release of the topologic constraint was expected. We show that locked TALEs indeed have diminished DNA binding and regain full transcriptional activity by stimulation with the rapamycin ligand or site-specific proteolysis of the peptide linker, with much higher level of activation than rapamycin-induced heterodimerization. Additionally, we demonstrated reversibility, activation of genomic targets and implemented logic gates based on combinations of protein cyclization, proteolytic cleavage and ligand-induced dimerization, where the strongest fold induction was achieved by the proteolytic cleavage of a repression domain from a linear TALE.
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Registered trials
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