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Bacterial gene control by DNA looping using engineered dimeric transcription activator like effector (TALE) proteins.


ABSTRACT: Genetic switches must alternate between states whose probabilities are dependent on regulatory signals. Classical examples of transcriptional control in bacteria depend on repressive DNA loops anchored by proteins whose structures are sensitive to small molecule inducers or co-repressors. We are interested in exploiting these natural principles to engineer artificial switches for transcriptional control of bacterial genes. Here, we implement designed homodimeric DNA looping proteins ('Transcription Activator-Like Effector Dimers'; TALEDs) for this purpose in living bacteria. Using well-studied FKBP dimerization domains, we build switches that mimic regulatory characteristics of classical Escherichia coli lactose, galactose and tryptophan operon promoters, including induction or co-repression by small molecules. Engineered DNA looping using TALEDs is thus a new approach to tuning gene expression in bacteria. Similar principles may also be applicable for gene control in eukaryotes.

SUBMITTER: Becker NA 

PROVIDER: S-EPMC5861415 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Bacterial gene control by DNA looping using engineered dimeric transcription activator like effector (TALE) proteins.

Becker Nicole A NA   Schwab Tanya L TL   Clark Karl J KJ   Maher L James LJ  

Nucleic acids research 20180301 5


Genetic switches must alternate between states whose probabilities are dependent on regulatory signals. Classical examples of transcriptional control in bacteria depend on repressive DNA loops anchored by proteins whose structures are sensitive to small molecule inducers or co-repressors. We are interested in exploiting these natural principles to engineer artificial switches for transcriptional control of bacterial genes. Here, we implement designed homodimeric DNA looping proteins ('Transcript  ...[more]

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