Transcription factors control the fate of a cell by regulating the expression of genes and regulatory networks. Recent successes in inducing pluripotency in terminally differentiated cells as well as directing differentiation with natural transcription factors has lent credence to the efforts that aim to direct cell fate with rationally designed transcription factors. Because DNA-binding factors are modular in design, they can be engineered to target specific genomic sequences and perform pre-programmed regulatory functions upon binding. Such precision-tailored factors can serve as molecular tools to reprogramme or differentiate cells in a targeted manner. Using different types of engineered DNA binders, both regulatory transcriptional controls of gene networks, as well as permanent alteration of genomic content, can be implemented to study cell fate decisions. In the present review, we describe the current state of the art in artificial transcription factor design and the exciting prospect of employing artificial DNA-binding factors to manipulate the transcriptional networks as well as epigenetic landscapes that govern cell fate.
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September 2014
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Review Article|
August 22 2014
Controlling gene networks and cell fate with precision-targeted DNA-binding proteins and small-molecule-based genome readers
Asuka Eguchi;
Asuka Eguchi
*Graduate Program in Cellular and Molecular Biology, University of Wisconsin-Madison, 1525 Linden Drive, Madison, WI 53706, U.S.A.
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Garrett O. Lee;
Garrett O. Lee
*Graduate Program in Cellular and Molecular Biology, University of Wisconsin-Madison, 1525 Linden Drive, Madison, WI 53706, U.S.A.
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Fang Wan;
Fang Wan
†The Genome Center of Wisconsin, University of Wisconsin-Madison, 425 Henry Mall, Madison, WI 53706, U.S.A.
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Graham S. Erwin;
Graham S. Erwin
‡Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI 53706, U.S.A.
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Aseem Z. Ansari
Aseem Z. Ansari
1
†The Genome Center of Wisconsin, University of Wisconsin-Madison, 425 Henry Mall, Madison, WI 53706, U.S.A.
‡Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI 53706, U.S.A.
1To whom correspondence should be addressed (email ansari@biochem.wisc.edu).
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Publisher: Portland Press Ltd
Received:
March 25 2014
Revision Received:
June 17 2014
Accepted:
June 27 2014
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2014 Biochemical Society
2014
Biochem J (2014) 462 (3): 397–413.
Article history
Received:
March 25 2014
Revision Received:
June 17 2014
Accepted:
June 27 2014
Citation
Asuka Eguchi, Garrett O. Lee, Fang Wan, Graham S. Erwin, Aseem Z. Ansari; Controlling gene networks and cell fate with precision-targeted DNA-binding proteins and small-molecule-based genome readers. Biochem J 15 September 2014; 462 (3): 397–413. doi: https://doi.org/10.1042/BJ20140400
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