title: Controlling gene networks and cell fate with precision-targeted DNA-binding proteins and small-molecule-based genome readers.
abstract: 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.
authors.affiliation: *Graduate Program in Cellular and Molecular Biology, University of Wisconsin-Madison, 1525 Linden Drive, Madison, WI 53706, U.S.A.
authors.forename: Asuka
authors.initials: A
authors.lastname: Eguchi
authors.affiliation: *Graduate Program in Cellular and Molecular Biology, University of Wisconsin-Madison, 1525 Linden Drive, Madison, WI 53706, U.S.A.
authors.forename: Garrett O
authors.initials: GO
authors.lastname: Lee
authors.affiliation: †The Genome Center of Wisconsin, University of Wisconsin-Madison, 425 Henry Mall, Madison, WI 53706, U.S.A.
authors.forename: Fang
authors.initials: F
authors.lastname: Wan
authors.affiliation: ‡Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI 53706, U.S.A.
authors.forename: Graham S
authors.initials: GS
authors.lastname: Erwin
authors.forename: Aseem Z
authors.initials: AZ
authors.lastname: Ansari
mesh_terms: D064130:CRISPR-Associated Proteins / Q000502:physiology; D004268:DNA-Binding Proteins / Q000502:physiology*; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks / Q000502:physiology*; D009757:Nylons / Q000737:chemistry / Q000378:metabolism; D015202:Protein Engineering; D017434:Protein Structure, Tertiary; D014157:Transcription Factors / Q000378:metabolism*; D016335:Zinc Fingers / Q000502:physiology
chemical_list: D064130:CRISPR-Associated Proteins; D004268:DNA-Binding Proteins; D009757:Nylons; D014157:Transcription Factors