Summary
Artificial transcription factors (ATFs) are designed to mimic natural transcription factors in the control of gene expression and are comprised of domains for DNA binding and gene regulation. ATF domains are modular, interchangeable, and can be composed of protein-based or nonpeptidic moieties, yielding DNA-interacting regulatory molecules that can either activate or inhibit transcription. Sequence-specific targeting is a key determinant in ATF activity, and DNA-binding domains such as natural zinc fingers and synthetic polyamides have emerged as useful DNA targeting molecules. Defining the comprehensive DNA binding specificity of these targeting molecules for accurate manipulations of the genome can be achieved using cognate site identifier DNA microarrays to explore the entire sequence space of binding sites. Design of ATFs that regulate gene expression with temporal control will generate important molecular tools to probe cell- and tissue-specific gene regulation and to function as potential therapeutic agents.
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Acknowledgments
The authors thank Karl Hauschild and Clayton Carlson for reviewing the manuscript and Laura Vanderploeg for help with figures. This work was supported by the National Institutes of Health grant R01 GM069420 to (AZA), University of Wisconsin Innovation and Economic Development Research Program (AZA and MSO), National Foundation—March of Dimes (AZA), US Department of Agriculture—Hatch/McIntire/Stennis grant (AZA), the Greater Milwaukee Foundation—Shaw Scientist Award (AZA), and Computation and Informatics in Biology and Medicine Training Grant T15LM007359 (CLW).
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Ozers, M.S., Warren, C.L., Ansari, A.Z. (2009). Determining DNA Sequence Specificity of Natural and Artificial Transcription Factors by Cognate Site Identifier Analysis. In: Foote, R., Lee, J. (eds) Micro and Nano Technologies in Bioanalysis. Methods in Molecular Biology™, vol 544. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59745-483-4_41
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DOI: https://doi.org/10.1007/978-1-59745-483-4_41
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