Abstract
Zinc fingers are the most abundant DNA-binding motifs encoded by eukaryotic genomes and one of the best understood DNA-recognition domains. Each zinc finger typically binds a 3-nt target sequence, and it is possible to engineer zinc-finger arrays (ZFAs) that recognize extended DNA sequences by linking together individual zinc fingers. Engineered zinc-finger proteins have proven to be valuable tools for gene regulation and genome modification because they target specific sites in a genome. Here we describe ZiFDB (Zinc Finger Database; http://bindr.gdcb.iastate.edu/ZiFDB), a web-accessible resource that compiles information on individual zinc fingers and engineered ZFAs. To enhance its utility, ZiFDB is linked to the output from ZiFiT--a software package that assists biologists in finding sites within target genes for engineering zinc-finger proteins. For many molecular biologists, ZiFDB will be particularly valuable for determining if a given ZFA (or portion thereof) has previously been constructed and whether or not it has the requisite DNA-binding activity for their experiments. ZiFDB will also be a valuable resource for those scientists interested in better understanding how zinc-finger proteins recognize target DNA.
MeSH Terms
Binding Sites
DNA/chemistry
DNA-Binding Proteins/chemistry,genetics
Databases, Protein
Oligonucleotide Array Sequence Analysis
Protein Engineering
Transcription Factors/chemistry,genetics
User-Computer Interface
Zinc Fingers
Chemicals
DNA-Binding Proteins
Transcription Factors
DNA
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Fu Fengli
Department of Genetics, Development & Cell Biology, 1043 Roy J. Carver Co-Laboratory, Iowa State University, Ames, Iowa 50011, USA.
Sander Jeffry D
Maeder Morgan
Thibodeau-Beganny Stacey
Joung J Keith
Dobbs Drena
Miller Leslie
Voytas Daniel F
References (21)
21 references, click to expand
-
A bacterial two-hybrid selection system for studying protein-DNA and protein-protein interactions.
Proc Natl Acad Sci U S A. 2000 Jun 20;97(13):7382-7
PMID: 10852947
-
Zinc-finger nucleases: the next generation emerges.
Mol Ther. 2008 Jul;16(7):1200-7
PMID: 18545224
-
Insights into the molecular recognition of the 5'-GNN-3' family of DNA sequences by zinc finger domains.
J Mol Biol. 2000 Nov 3;303(4):489-502
PMID: 11054286
-
Synthetic zinc finger transcription factor action at an endogenous chromosomal site. Activation of the human erythropoietin gene.
J Biol Chem. 2000 Oct 27;275(43):33850-60
PMID: 10913152
-
Regulation of an endogenous locus using a panel of designed zinc finger proteins targeted to accessible chromatin regions. Activation of vascular endothelial growth factor A.
J Biol Chem. 2001 Apr 6;276(14):11323-34
PMID: 11145970
-
Development of zinc finger domains for recognition of the 5'-ANN-3' family of DNA sequences and their use in the construction of artificial transcription factors.
J Biol Chem. 2001 Aug 3;276(31):29466-78
PMID: 11340073
-
Validated zinc finger protein designs for all 16 GNN DNA triplet targets.
J Biol Chem. 2002 Feb 8;277(6):3850-6
PMID: 11726671
-
Rational design of artificial zinc-finger proteins using a nondegenerate recognition code table.
Biochemistry. 2002 Jun 4;41(22):7074-81
PMID: 12033941
-
Human zinc fingers as building blocks in the construction of artificial transcription factors.
Nat Biotechnol. 2003 Mar;21(3):275-80
PMID: 12592413
-
Highly specific zinc finger proteins obtained by directed domain shuffling and cell-based selection.
Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12271-6
PMID: 14527993
-
Toward rules relating zinc finger protein sequences and DNA binding site preferences.
Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7345-9
PMID: 1502144
-
A general strategy for selecting high-affinity zinc finger proteins for diverse DNA target sites.
Science. 1997 Jan 31;275(5300):657-61
PMID: 9005850
-
Synergy between adjacent zinc fingers in sequence-specific DNA recognition.
Proc Natl Acad Sci U S A. 1997 May 27;94(11):5617-21
PMID: 9159121
-
Toward controlling gene expression at will: selection and design of zinc finger domains recognizing each of the 5'-GNN-3' DNA target sequences.
Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):2758-63
PMID: 10077584
-
Development of zinc finger domains for recognition of the 5'-CNN-3' family DNA sequences and their use in the construction of artificial transcription factors.
J Biol Chem. 2005 Oct 21;280(42):35588-97
PMID: 16107335
-
Zinc Finger Tools: custom DNA-binding domains for transcription factors and nucleases.
Nucleic Acids Res. 2006 Jul 1;34(Web Server issue):W516-23
PMID: 16845061
-
Standardized reagents and protocols for engineering zinc finger nucleases by modular assembly.
Nat Protoc. 2006;1(3):1637-52
PMID: 17406455
-
Zinc Finger Targeter (ZiFiT): an engineered zinc finger/target site design tool.
Nucleic Acids Res. 2007 Jul;35(Web Server issue):W599-605
PMID: 17526515
-
Unexpected failure rates for modular assembly of engineered zinc fingers.
Nat Methods. 2008 May;5(5):374-5
PMID: 18446154
-
Rapid "open-source" engineering of customized zinc-finger nucleases for highly efficient gene modification.
Mol Cell. 2008 Jul 25;31(2):294-301
PMID: 18657511
-
DNA recognition by Cys2His2 zinc finger proteins.
Annu Rev Biophys Biomol Struct. 2000;29:183-212
PMID: 10940247