Rational design, selection and specificity of artificial transcription factors (ATFs): the influence of chromatin in target gene regulation.
Artificial Transcription Factors (ATFs) are engineered DNA-binding proteins designed to bind specific sequences of DNA. ATFs made of Zinc Finger (ZF) domains have been developed to regulate specific genes and phenotypes both in cells and whole organisms. Recently, an emerging application of engineered DNA-binding domains include the specific editing of the genome, the ability to specifically cut, recombine, modify DNA and image protein-nucleic acid interactions in living cells. In this review we will summarize the techniques used for the rational design, screening and functional selection of ZF proteins in mammalian cell systems and their applications in areas of biotechnology, functional genomics and molecular therapeutics. The in vivo specificity of the engineered ATFs will be discussed, with particular emphasis on epigenetic modifications influencing ATF-DNA interactions.
Blancafort
Pilar
P
Department of Pharmacology and the Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7365, USA. pilar_blancafort@med.unc.edu
Beltran
Adriana S
AS
D000818:Animals; D002843:Chromatin / Q000235:genetics*; D004247:DNA / Q000235:genetics; D015195:Drug Design; D005786:Gene Expression Regulation / Q000235:genetics*; D018390:Gene Targeting; D006801:Humans; D009690:Nucleic Acid Conformation; D010641:Phenotype; D015202:Protein Engineering; D014157:Transcription Factors / Q000235:genetics*; D016335:Zinc Fingers / Q000235:genetics
D002843:Chromatin; D014157:Transcription Factors; D004247:DNA