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- W2889969897 abstract "Gene-regulatory networks are ubiquitous in nature and critical for bottom-up engineering of synthetic networks. Transcriptional repression is a fundamental function that can be tuned at the level of DNA, protein, and cooperative protein–protein interactions, necessitating high-throughput experimental approaches for in-depth characterization. Here, we used a cell-free system in combination with a high-throughput microfluidic device to comprehensively study the different tuning mechanisms of a synthetic zinc-finger repressor library, whose affinity and cooperativity can be rationally engineered. The device is integrated into a comprehensive workflow that includes determination of transcription-factor binding-energy landscapes and mechanistic modeling, enabling us to generate a library of well-characterized synthetic transcription factors and corresponding promoters, which we then used to build gene-regulatory networks de novo. The well-characterized synthetic parts and insights gained should be useful for rationally engineering gene-regulatory networks and for studying the biophysics of transcriptional regulation." @default.
- W2889969897 created "2018-09-27" @default.
- W2889969897 creator A5032517726 @default.
- W2889969897 creator A5036658946 @default.
- W2889969897 creator A5087352392 @default.
- W2889969897 date "2019-03-08" @default.
- W2889969897 modified "2023-10-10" @default.
- W2889969897 title "Cell-free gene-regulatory network engineering with synthetic transcription factors" @default.
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- W2889969897 doi "https://doi.org/10.1073/pnas.1816591116" @default.
- W2889969897 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6442555" @default.
- W2889969897 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30850530" @default.
- W2889969897 hasPublicationYear "2019" @default.
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