zinc fingers

Summary

Summary: Motifs in DNA- and RNA-binding proteins whose amino acids are folded into a single structural unit around a zinc atom. In the classic zinc finger, one zinc atom is bound to two cysteines and two histidines. In between the cysteines and histidines are 12 residues which form a DNA binding fingertip. By variations in the composition of the sequences in the fingertip and the number and spacing of tandem repeats of the motif, zinc fingers can form a large number of different sequence specific binding sites.

Top Publications

  1. ncbi Genome editing with engineered zinc finger nucleases
    Fyodor D Urnov
    Sangamo Biosciences Inc, Richmond, California 94804, USA
    Nat Rev Genet 11:636-46. 2010
  2. pmc Efficient targeting of expressed and silent genes in human ESCs and iPSCs using zinc-finger nucleases
    Dirk Hockemeyer
    The Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA
    Nat Biotechnol 27:851-7. 2009
  3. pmc Targeted genome editing across species using ZFNs and TALENs
    Andrew J Wood
    Howard Hughes Medical Institute HHMI, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720 3204, USA
    Science 333:307. 2011
  4. ncbi An improved zinc-finger nuclease architecture for highly specific genome editing
    Jeffrey C Miller
    Sangamo BioSciences, Inc, Pt Richmond Tech Center, 501 Canal Blvd, Suite A100 Richmond, California 94804, USA
    Nat Biotechnol 25:778-85. 2007
  5. pmc Establishment of HIV-1 resistance in CD4+ T cells by genome editing using zinc-finger nucleases
    Elena E Perez
    Abramson Family Cancer Research Institute, Department of Pathology and Laboratory Medicine, 421 Curie Blvd, Room 554, BRB II III, Philadelphia, Pennsylvania 19104 6160, USA
    Nat Biotechnol 26:808-16. 2008
  6. pmc Revealing off-target cleavage specificities of zinc-finger nucleases by in vitro selection
    Vikram Pattanayak
    Department of Chemistry and Chemical Biology, and Howard Hughes Medical Institute, Harvard University, Cambridge, Massachusetts, USA
    Nat Methods 8:765-70. 2011
  7. ncbi Highly efficient endogenous human gene correction using designed zinc-finger nucleases
    Fyodor D Urnov
    Sangamo BioSciences, Inc, Pt Richmond Tech Center 501, Canal Blvd, Suite A100 Richmond, California 94804, USA
    Nature 435:646-51. 2005
  8. ncbi PRDM9 is a major determinant of meiotic recombination hotspots in humans and mice
    F Baudat
    Institut de Genetique Humaine, UPR1142, CNRS, Montpellier, France
    Science 327:836-40. 2010
  9. pmc Knockout rats via embryo microinjection of zinc-finger nucleases
    Aron M Geurts
    Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, WI 52336, USA
    Science 325:433. 2009
  10. ncbi An unbiased genome-wide analysis of zinc-finger nuclease specificity
    Richard Gabriel
    Department of Translational Oncology, National Center for Tumor Diseases NCT and German Cancer Research Center DKFZ, Heidelberg, Germany
    Nat Biotechnol 29:816-23. 2011

Detail Information

Publications247 found, 100 shown here

  1. ncbi Genome editing with engineered zinc finger nucleases
    Fyodor D Urnov
    Sangamo Biosciences Inc, Richmond, California 94804, USA
    Nat Rev Genet 11:636-46. 2010
    ..Such 'genome editing' is now established in human cells and a number of model organisms, thus opening the door to a range of new experimental and therapeutic possibilities...
  2. pmc Efficient targeting of expressed and silent genes in human ESCs and iPSCs using zinc-finger nucleases
    Dirk Hockemeyer
    The Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA
    Nat Biotechnol 27:851-7. 2009
    ..Finally, we targeted the PITX3 gene, demonstrating that ZFNs can be used to generate reporter cells by targeting non-expressed genes in hESCs and hiPSCs...
  3. pmc Targeted genome editing across species using ZFNs and TALENs
    Andrew J Wood
    Howard Hughes Medical Institute HHMI, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720 3204, USA
    Science 333:307. 2011
    ....
  4. ncbi An improved zinc-finger nuclease architecture for highly specific genome editing
    Jeffrey C Miller
    Sangamo BioSciences, Inc, Pt Richmond Tech Center, 501 Canal Blvd, Suite A100 Richmond, California 94804, USA
    Nat Biotechnol 25:778-85. 2007
    ..This architecture provides a general means for improving the specificity of ZFNs as gene modification reagents...
  5. pmc Establishment of HIV-1 resistance in CD4+ T cells by genome editing using zinc-finger nucleases
    Elena E Perez
    Abramson Family Cancer Research Institute, Department of Pathology and Laboratory Medicine, 421 Curie Blvd, Room 554, BRB II III, Philadelphia, Pennsylvania 19104 6160, USA
    Nat Biotechnol 26:808-16. 2008
    ..Thus adoptive transfer of ex vivo expanded CCR5 ZFN-modified autologous CD4(+) T cells in HIV patients is an attractive approach for the treatment of HIV-1 infection...
  6. pmc Revealing off-target cleavage specificities of zinc-finger nucleases by in vitro selection
    Vikram Pattanayak
    Department of Chemistry and Chemical Biology, and Howard Hughes Medical Institute, Harvard University, Cambridge, Massachusetts, USA
    Nat Methods 8:765-70. 2011
    ..Our findings establish an energy compensation model of ZFN specificity in which excess binding energy contributes to off-target ZFN cleavage and suggest strategies for the improvement of future ZFN design...
  7. ncbi Highly efficient endogenous human gene correction using designed zinc-finger nucleases
    Fyodor D Urnov
    Sangamo BioSciences, Inc, Pt Richmond Tech Center 501, Canal Blvd, Suite A100 Richmond, California 94804, USA
    Nature 435:646-51. 2005
    ..We observe comparably high frequencies in human T cells, raising the possibility of strategies based on zinc-finger nucleases for the treatment of disease...
  8. ncbi PRDM9 is a major determinant of meiotic recombination hotspots in humans and mice
    F Baudat
    Institut de Genetique Humaine, UPR1142, CNRS, Montpellier, France
    Science 327:836-40. 2010
    ..Third, allelic variants of PRDM9 zinc fingers are significantly associated with variability in genome-wide hotspot usage among humans...
  9. pmc Knockout rats via embryo microinjection of zinc-finger nucleases
    Aron M Geurts
    Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, WI 52336, USA
    Science 325:433. 2009
    ..Our data demonstrate the feasibility of targeted gene disruption in multiple rat strains within 4 months time, paving the way to a humanized monoclonal antibody platform and additional human disease models...
  10. ncbi An unbiased genome-wide analysis of zinc-finger nuclease specificity
    Richard Gabriel
    Department of Translational Oncology, National Center for Tumor Diseases NCT and German Cancer Research Center DKFZ, Heidelberg, Germany
    Nat Biotechnol 29:816-23. 2011
    ..Comprehensive mapping of ZFN activity in vivo will facilitate the broad application of these reagents in translational research...
  11. pmc Targeted gene knockout by direct delivery of zinc-finger nuclease proteins
    Thomas Gaj
    The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California, USA
    Nat Methods 9:805-7. 2012
    ....
  12. pmc Selection-free zinc-finger-nuclease engineering by context-dependent assembly (CoDA)
    Jeffry D Sander
    Molecular Pathology Unit and Center for Cancer Research, Massachusetts General Hospital, Charlestown, Massachusetts, USA
    Nat Methods 8:67-9. 2011
    ..The simplicity and efficacy of CoDA will enable broad adoption of ZFN technology and make possible large-scale projects focused on multigene pathways or genome-wide alterations...
  13. pmc Heritable targeted gene disruption in zebrafish using designed zinc-finger nucleases
    Yannick Doyon
    Sangamo BioSciences, Inc, Pt Richmond Tech Center, 501 Canal Blvd, Suite A100, Richmond, California 94804, USA
    Nat Biotechnol 26:702-8. 2008
    ..The frequency and precision of gene-disruption events observed suggest that this approach should be applicable to any loci in zebrafish or in other organisms that allow mRNA delivery into the fertilized egg...
  14. pmc Genome engineering with zinc-finger nucleases
    Dana Carroll
    Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, Utah 84112 5650, USA
    Genetics 188:773-82. 2011
    ..The bright prospects for future applications of ZFNs, including human gene therapy, are discussed...
  15. pmc Targeted gene inactivation in zebrafish using engineered zinc-finger nucleases
    Xiangdong Meng
    Program in Gene Function and Expression, University of Massachusetts Medical School, Lazare Research Building, 6th Floor, 364 Plantation St, Worcester, Massachusetts 01605, USA
    Nat Biotechnol 26:695-701. 2008
    ..The use of engineered ZFNs to introduce heritable mutations into a genome obviates the need for embryonic stem cell lines and should be applicable to most animal species for which early-stage embryos are easily accessible...
  16. pmc High-frequency genome editing using ssDNA oligonucleotides with zinc-finger nucleases
    Fuqiang Chen
    Sigma Aldrich Biotechnology, St Louis, Missouri, USA
    Nat Methods 8:753-5. 2011
    ....
  17. pmc Human hematopoietic stem/progenitor cells modified by zinc-finger nucleases targeted to CCR5 control HIV-1 in vivo
    Nathalia Holt
    Keck School of Medicine of the University of Southern California, Los Angeles, California, USA
    Nat Biotechnol 28:839-47. 2010
    ..The demonstration that a minority of CCR5(-/-) HSPCs can populate an infected animal with HIV-1-resistant, CCR5(-/-) progeny supports the use of ZFN-modified autologous hematopoietic stem cells as a clinical approach to treating HIV-1...
  18. pmc An optimized two-finger archive for ZFN-mediated gene targeting
    Ankit Gupta
    Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, USA
    Nat Methods 9:588-90. 2012
    ..Using this archive, we introduced lesions at 9 of 11 target sites in the zebrafish genome...
  19. ncbi Enhancing zinc-finger-nuclease activity with improved obligate heterodimeric architectures
    Yannick Doyon
    Sangamo BioSciences, Richmond, California, USA
    Nat Methods 8:74-9. 2011
    ..These ZFN architectures provide a general means for obtaining highly efficient and specific genome modification...
  20. pmc Prdm9 controls activation of mammalian recombination hotspots
    Emil D Parvanov
    The Jackson Laboratory, Bar Harbor, ME 04609, USA
    Science 327:835. 2010
    ..The identification of Prdm9 as a protein regulating mammalian recombination hotspots initiates molecular studies of this important biological control system...
  21. pmc In vivo genome editing restores haemostasis in a mouse model of haemophilia
    Hojun Li
    Division of Hematology, CTRB 5000, Children s Hospital of Philadelphia, 3501 Civic Center Boulevard, Philadelphia, Pennsylvania 19104, USA
    Nature 475:217-21. 2011
    ..Thus, ZFN-driven gene correction can be achieved in vivo, raising the possibility of genome editing as a viable strategy for the treatment of genetic disease...
  22. pmc In situ genetic correction of the sickle cell anemia mutation in human induced pluripotent stem cells using engineered zinc finger nucleases
    Vittorio Sebastiano
    Department of Pathology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford California, USA
    Stem Cells 29:1717-26. 2011
    ..Our results provide an important proof of principle that ZFNs can be used to produce gene-corrected human iPSCs that could be used for therapeutic applications...
  23. pmc SETDB1: a novel KAP-1-associated histone H3, lysine 9-specific methyltransferase that contributes to HP1-mediated silencing of euchromatic genes by KRAB zinc-finger proteins
    David C Schultz
    The Wistar Institute, Philadelphia, Pennsylvania 19104, USA
    Genes Dev 16:919-32. 2002
    ..Thus, KAP-1 is a molecular scaffold that is targeted by KRAB-ZFPs to specific loci and coordinates both histone methylation and the deposition of HP1 proteins to silence gene expression...
  24. pmc Rapid "open-source" engineering of customized zinc-finger nucleases for highly efficient gene modification
    Morgan L Maeder
    Molecular Pathology Unit and Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA 02129, USA
    Mol Cell 31:294-301. 2008
    ..In summary, OPEN provides an "open-source" method for rapidly engineering highly active zinc-finger arrays, thereby enabling broader practice, development, and application of ZFN technology for biological research and gene therapy...
  25. ncbi Gene editing in human stem cells using zinc finger nucleases and integrase-defective lentiviral vector delivery
    Angelo Lombardo
    San Raffaele Telethon Institute for Gene Therapy, Via Olgettina, 58, 20132 Milan, Italy
    Nat Biotechnol 25:1298-306. 2007
    ....
  26. ncbi Structure-based redesign of the dimerization interface reduces the toxicity of zinc-finger nucleases
    Michal Szczepek
    Charite Medical School, Institute of Virology CBF, 12203 Berlin, Germany
    Nat Biotechnol 25:786-93. 2007
    ..Cell-based recombination assays confirmed that the modified ZFNs were as active as the original ZFNs but elicit significantly less genotoxicity. The improved safety profile may facilitate therapeutic application of the ZFN technology...
  27. pmc Targeted genome editing in human cells with zinc finger nucleases constructed via modular assembly
    Hye Joo Kim
    Department of Chemistry, Seoul National University, Gwanak Gu, Seoul 151 742, South Korea
    Genome Res 19:1279-88. 2009
    ..Here we describe an efficient and easy-to-practice modular-assembly method using publicly available zinc fingers to make ZFNs that can modify the DNA sequences of predetermined genomic sites in human cells...
  28. ncbi A rapid and general assay for monitoring endogenous gene modification
    Dmitry Y Guschin
    Sangamo BioSciences, Inc, Richmond, CA, USA
    Methods Mol Biol 649:247-56. 2010
    ..The assay is based on the ability of the Surveyor nuclease to selectively cleave distorted duplex DNA formed via cross-annealing of mutated and wild-type sequence...
  29. ncbi Enhancing gene targeting with designed zinc finger nucleases
    Marina Bibikova
    Department of Biochemistry, University of Utah School of Medicine, 20 North 1900 East, Salt Lake City, UT 84132 3201, USA
    Science 300:764. 2003
  30. ncbi The discovery of zinc fingers and their applications in gene regulation and genome manipulation
    Aaron Klug
    MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom
    Annu Rev Biochem 79:213-31. 2010
    ..Whereas other DNA binding proteins generally make use of the two-fold symmetry of the double helix, zinc fingers can be linked linearly in tandem to recognize nucleic acid sequences of varying lengths...
  31. ncbi Targeted integration in rat and mouse embryos with zinc-finger nucleases
    Xiaoxia Cui
    Sigma Advanced Genetic Engineering Labs, Sigma Aldrich Biotechnology, St Louis, Missouri, USA
    Nat Biotechnol 29:64-7. 2011
    ..The same strategy can potentially be applied to many other species for which genetic engineering tools are needed...
  32. pmc Targeted chromosomal cleavage and mutagenesis in Drosophila using zinc-finger nucleases
    Marina Bibikova
    Department of Biochemistry, University of Utah School of Medicine, Medical Research and Education Building, 20 North 1900 East, Salt Lake City, UT 84132, USA
    Genetics 161:1169-75. 2002
    ..ZFNs) are hybrids between a nonspecific DNA-cleavage domain and a DNA-binding domain composed of Cys(2)His(2) zinc fingers. Because zinc fingers can be manipulated to recognize a broad range of sequences, these enzymes have the ..
  33. pmc Structural classification of zinc fingers: survey and summary
    S Sri Krishna
    Department of Biochemistry, University of Texas, Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390 9050, USA
    Nucleic Acids Res 31:532-50. 2003
    b>Zinc fingers are small protein domains in which zinc plays a structural role contributing to the stability of the domain...
  34. pmc Targeted genome modification in mice using zinc-finger nucleases
    Iara D Carbery
    Sigma Advanced Genetic Engineering Labs, Sigma Aldrich Biotechnology, St Louis, MO 63146, USA
    Genetics 186:451-9. 2010
    ..We conclude that ZFN technology is an efficient and convenient alternative to conventional gene targeting and will greatly facilitate the rapid creation of mouse models and functional genomics research...
  35. pmc Targeted chromosomal deletions in human cells using zinc finger nucleases
    Hyung Joo Lee
    Department of Chemistry, Seoul National University, Seoul, South Korea
    Genome Res 20:81-9. 2010
    ..Thus, ZFN-induced genomic deletions should be broadly useful as a novel method in biomedical research, biotechnology, and gene therapy...
  36. doi Unexpected failure rates for modular assembly of engineered zinc fingers
    Cherie L Ramirez
    Nat Methods 5:374-5. 2008
  37. pmc Targeted chromosomal duplications and inversions in the human genome using zinc finger nucleases
    Hyung Joo Lee
    National Creative Research Initiatives Center for Genome Engineering, Department of Chemistry, Seoul National University, 599 Gwanak Ro, Seoul, South Korea
    Genome Res 22:539-48. 2012
    ..In addition, our method raises the possibility of correcting genetic defects caused by chromosomal rearrangements and holds new promise in gene and cell therapy...
  38. pmc Arabidopsis Cys2/His2-type zinc-finger proteins function as transcription repressors under drought, cold, and high-salinity stress conditions
    Hideki Sakamoto
    Biological Resources Division, Japan International Research Center for Agricultural Sciences, Tsukuba, Ibaraki 305 8686, Japan
    Plant Physiol 136:2734-46. 2004
    ..These results suggest that AZF2 and STZ function as transcriptional repressors to increase stress tolerance following growth retardation...
  39. ncbi Chimeric nucleases stimulate gene targeting in human cells
    Matthew H Porteus
    Department of Biology, California Institute of Technology, Pasadena CA 91125, USA
    Science 300:763. 2003
  40. ncbi Zinc finger proteins: new insights into structural and functional diversity
    J H Laity
    Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Curr Opin Struct Biol 11:39-46. 2001
    ....
  41. pmc Efficient targeted gene disruption in the soma and germ line of the frog Xenopus tropicalis using engineered zinc-finger nucleases
    John J Young
    Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720 3200, USA
    Proc Natl Acad Sci U S A 108:7052-7. 2011
    ..Because ZFNs can be designed against any locus, our data provide a generally applicable protocol for gene disruption in Xenopus...
  42. pmc Gene targeting of a disease-related gene in human induced pluripotent stem and embryonic stem cells
    Jizhong Zou
    Stem Cell Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Cell Stem Cell 5:97-110. 2009
    ..Our study provides the first demonstration of HR-mediated gene targeting in hiPSCs and shows the power of ZFNs for inducing specific genetic modifications in hiPSCs, as well as hESCs...
  43. pmc Accelerated evolution of the Prdm9 speciation gene across diverse metazoan taxa
    Peter L Oliver
    Medical Research Council Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom
    PLoS Genet 5:e1000753. 2009
    ..Mouse Prdm9 encodes a protein with a KRAB motif, a histone methyltransferase domain and several zinc fingers. The difference of a single zinc finger distinguishes Prdm9 alleles that cause hybrid sterility from those that ..
  44. pmc Zinc finger protein-dependent and -independent contributions to the in vivo off-target activity of zinc finger nucleases
    Ankit Gupta
    Program in Gene Function and Expression, Department of Biochemistry and Molecular Pharmacology and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
    Nucleic Acids Res 39:381-92. 2011
    ..Surprisingly, we observed that both the specificity of the incorporated zinc fingers and the choice of the engineered nuclease domain could independently influence the fidelity of these ZFNs...
  45. ncbi Surrogate reporters for enrichment of cells with nuclease-induced mutations
    Hyojin Kim
    Department of Chemistry, Seoul National University, Gwanak Gu, Seoul, South Korea
    Nat Methods 8:941-3. 2011
    ..Here we show that transiently transfected episomal reporters encoding fluorescent proteins can be used as surrogate genes for the efficient enrichment of endogenous gene-modified cells by flow cytometry...
  46. pmc High-frequency modification of plant genes using engineered zinc-finger nucleases
    Jeffrey A Townsend
    Department of Genetics, Development and Cell Biology, Iowa State University, Ames, Iowa 50011, USA
    Nature 459:442-5. 2009
    ..More than 40% of recombinant plants had modifications in multiple SuR alleles. The observed high frequency of gene targeting indicates that it is now possible to efficiently make targeted sequence changes in endogenous plant genes...
  47. pmc ZiFiT (Zinc Finger Targeter): an updated zinc finger engineering tool
    Jeffry D Sander
    Molecular Pathology Unit, Center for Cancer Research, and Center for Computational and Integrative Biology, Massachusetts General Hospital, Charlestown, MA 02129, USA
    Nucleic Acids Res 38:W462-8. 2010
    ..ZiFiT is freely available on the web without registration at http://bindr.gdcb.iastate.edu/ZiFiT/...
  48. ncbi The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation
    Kazuhisa Nakashima
    Department of Molecular Genetics and Program in Genes and Development, M D Anderson Cancer Center, University of Texas, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    Cell 108:17-29. 2002
    ..Thus, Osx acts downstream of Runx2/Cbfa1. Because Osx null preosteoblasts express typical chondrocyte marker genes, we propose that Runx2/Cbfa1-expressing preosteoblasts are still bipotential cells...
  49. ncbi Zinc finger-DNA recognition: crystal structure of a Zif268-DNA complex at 2.1 A
    N P Pavletich
    Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205
    Science 252:809-17. 1991
    ..The crystal structure of a complex containing the three zinc fingers from Zif268 (a mouse immediate early protein) and a consensus DNA-binding site has been determined at 2...
  50. pmc Global analysis of Drosophila Cys₂-His₂ zinc finger proteins reveals a multitude of novel recognition motifs and binding determinants
    Metewo Selase Enuameh
    Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
    Genome Res 23:928-40. 2013
    ..These hybrids of natural and artificial fingers can be used to create functional zinc finger nucleases for editing vertebrate genomes...
  51. pmc Functional genomics, proteomics, and regulatory DNA analysis in isogenic settings using zinc finger nuclease-driven transgenesis into a safe harbor locus in the human genome
    Russell C DeKelver
    Sangamo BioSciences, Inc, Point Richmond Tech Center, Richmond, California 94804, USA
    Genome Res 20:1133-42. 2010
    ....
  52. pmc Highly active zinc-finger nucleases by extended modular assembly
    Mital S Bhakta
    Genome Center and Department of Biochemistry and Molecular Medicine, University of California, Davis, CA 95616, USA
    Genome Res 23:530-8. 2013
    ..These results suggest that, when used appropriately, MA ZFNs are able to target more DNA sequences with higher success rates than other current methods...
  53. pmc Sp1- and Krüppel-like transcription factors
    Joanna Kaczynski
    Gastroenterology Research Unit, Mayo Clinic, Rochester, MN 55901, USA
    Genome Biol 4:206. 2003
    ..Sp1-like/KLF proteins have highly conserved carboxy-terminal zinc-finger domains that function in DNA binding. The amino terminus, containing the transcription activation domain, can vary significantly between family members...
  54. pmc Directed evolution of an enhanced and highly efficient FokI cleavage domain for zinc finger nucleases
    Jing Guo
    The Skaggs Institute for Chemical Biology and Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    J Mol Biol 400:96-107. 2010
    ..This enhanced and highly efficient cleavage domain will aid in a variety of ZFN applications in medicine and biology...
  55. pmc Repression domains of class II ERF transcriptional repressors share an essential motif for active repression
    M Ohta
    Gene Discovery Research Center, National Institute of Advanced Industrial Science and Technology AIST, Central 6, Tsukuba 305 8566, Japan
    Plant Cell 13:1959-68. 2001
    ..These zinc finger proteins functioned as repressors, and their repression domains were identified as regions that contained an EAR motif...
  56. ncbi Transient cold shock enhances zinc-finger nuclease-mediated gene disruption
    Yannick Doyon
    Sangamo BioSciences, Richmond, California, USA
    Nat Methods 7:459-60. 2010
    ..Here we show that transient hypothermia generally and robustly increased the level of stable, ZFN-induced gene disruption, thereby providing a simple technique to enhance the experimental efficacy of ZFNs...
  57. pmc Progress and prospects: zinc-finger nucleases as gene therapy agents
    D Carroll
    Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112 5650, USA
    Gene Ther 15:1463-8. 2008
    ..New tools are available for the design and testing of ZFNs for new target genes. Applications of ZFNs to stem cells have been described, and genuine gene therapy trials appear to be on the immediate horizon...
  58. pmc Evaluation and application of modularly assembled zinc-finger nucleases in zebrafish
    Cong Zhu
    Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, MA 01605, USA
    Development 138:4555-64. 2011
    ..This work provides a resource to allow targeted germline gene inactivation in zebrafish and highlights the benefit of a definitive reverse genetic strategy to reveal gene function...
  59. pmc Gene targeting by homologous recombination in mouse zygotes mediated by zinc-finger nucleases
    Melanie Meyer
    Institute for Developmental Genetics, Helmholtz Center Munich, Munich, Germany
    Proc Natl Acad Sci U S A 107:15022-6. 2010
    ..These findings enable the manipulation of the mammalian germ line in a single step in zygotes, independent of ES cells...
  60. pmc Efficient gene targeting in Drosophila by direct embryo injection with zinc-finger nucleases
    Kelly J Beumer
    Department of Biochemistry, University of Utah School of Medicine, 15 North Medical Drive East, Salt Lake City, UT 84112 5650, USA
    Proc Natl Acad Sci U S A 105:19821-6. 2008
    ..The injection procedure is much more rapid than earlier approaches and makes possible the generation and recovery of targeted gene alterations at essentially any locus within 2 fly generations...
  61. pmc Generation of knockout rats with X-linked severe combined immunodeficiency (X-SCID) using zinc-finger nucleases
    Tomoji Mashimo
    Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University, Kyoto, Japan
    PLoS ONE 5:e8870. 2010
    ..Recently, zinc-finger nucleases (ZFNs) were successfully used to create genome-specific double-stranded breaks and thereby induce targeted gene mutations in a wide variety of organisms including plants, drosophila, zebrafish, etc...
  62. ncbi Zinc-finger nucleases: the next generation emerges
    Toni Cathomen
    Institute of Virology CBF, Charite Medical School, Berlin, Germany
    Mol Ther 16:1200-7. 2008
    ..In this paper we review recent advances in, and upcoming challenges for, this emerging technology and discuss future experimental work that will be needed to bring ZFNs safely into a clinical setting...
  63. pmc Adaptive evolution in zinc finger transcription factors
    Ryan O Emerson
    Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America
    PLoS Genet 5:e1000325. 2009
    ..These results suggest that the poly-ZF genes are a major source of new transcriptional repression activity in humans and other primates...
  64. pmc An exceptionally conserved transcriptional repressor, CTCF, employs different combinations of zinc fingers to bind diverged promoter sequences of avian and mammalian c-myc oncogenes
    G N Filippova
    Fred Hutchinson Cancer Research Center, Seattle, Washington 98104, USA
    Mol Cell Biol 16:2802-13. 1996
    ..e., c-myc) of different vertebrate species are regulated by the same factor and maintain similar expression patterns despite significant promoter sequence divergence...
  65. pmc A gene expression signature shared by human mature oocytes and embryonic stem cells
    Said Assou
    CHU Montpellier, Institute for Research in Biotherapy, Hopital Saint Eloi, Montpellier, F 34000 France
    BMC Genomics 10:10. 2009
    ..Comparison of the transcriptome of these two cell types may highlight genes that are involved in pluripotency initiation...
  66. ncbi The POZ domain: a conserved protein-protein interaction motif
    V J Bardwell
    Imperial Cancer Research Fund Laboratories, London, UK
    Genes Dev 8:1664-77. 1994
    ..We discuss the implications of multimerization for the function of POZ domain proteins...
  67. pmc Genome-wide survey and expression profiling of CCCH-zinc finger family reveals a functional module in macrophage activation
    Jian Liang
    Biomolecular Science Center, College of Medicine, University of Central Florida, Orlando, Florida, United States of America
    PLoS ONE 3:e2880. 2008
    ....
  68. ncbi The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion
    J Comijn
    Molecular Cell Biology Unit, Department of Molecular Biology, VIB Ghent University, B 9000, Ghent, Belgium
    Mol Cell 7:1267-78. 2001
    ..SIP1 therefore appears to be a promoter of invasion in malignant epithelial tumors...
  69. pmc KRAB-zinc finger proteins and KAP1 can mediate long-range transcriptional repression through heterochromatin spreading
    Anna C Groner
    School of Life Sciences, Ecole Polytechnique Federale de Lausanne EPFL, Lausanne, Switzerland
    PLoS Genet 6:e1000869. 2010
    ..This finding not only suggests auto-regulatory mechanisms in the control of KRAB-ZFP gene clusters, but also provides important cues for interpreting future genome-wide DNA binding data of KRAB-ZFPs and KAP1...
  70. ncbi Zinc finger proteins: getting a grip on RNA
    Raymond S Brown
    Division of Experimental Medicine, Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, 4 Blackfan Circle, Boston, MA 02115, USA
    Curr Opin Struct Biol 15:94-8. 2005
    ..Together, these results contrast the different ways that zinc finger proteins bind with high specificity to their RNA targets...
  71. pmc A maternal-zygotic effect gene, Zfp57, maintains both maternal and paternal imprints
    Xiajun Li
    Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
    Dev Cell 15:547-57. 2008
    ..The effects on genomic imprinting are consistent with the maternal-zygotic lethality of Zfp57 mutants...
  72. ncbi Characterization of a family of RanBP2-type zinc fingers that can recognize single-stranded RNA
    Cuong D Nguyen
    School of Molecular Bioscience, University of Sydney, Sydney, NSW, Australia
    J Mol Biol 407:273-83. 2011
    ..These data establish a subset of RanBP2-type ZnFs as a new family of ssRNA-binding motifs...
  73. ncbi GATA transcription factors in the developing and adult heart
    Sampsa Pikkarainen
    Department of Pharmacology and Toxicology, Faculty of Medicine, Biocenter Oulu, University of Oulu, P O Box 5000, FIN 90014 Oulu, Finland
    Cardiovasc Res 63:196-207. 2004
    ..The present review discusses current evidence of the role and regulation of GATA transcription factors in the heart, with an emphasis in the GATA-4 and development of cardiac hypertrophy...
  74. ncbi Tristetraprolin and other CCCH tandem zinc-finger proteins in the regulation of mRNA turnover
    P J Blackshear
    Office of Clinical Research and the Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    Biochem Soc Trans 30:945-52. 2002
    ..Together, the TTP family members should be capable of complex regulation of short-lived mRNAs containing this type of AU-rich instability motif...
  75. pmc p53 Gene repair with zinc finger nucleases optimised by yeast 1-hybrid and validated by Solexa sequencing
    Frank Herrmann
    EMBL CRG Systems Biology Research Unit, Centre for Genomic Regulation and UPF, Barcelona, Spain
    PLoS ONE 6:e20913. 2011
    ..Our Y1H system facilitates the generation and optimisation of novel, sequence-specific four- to six-finger peptides, and the p53-specific ZFN described here can be used to mutate or repair p53 in genomic loci...
  76. ncbi Evidence that tristetraprolin is a physiological regulator of granulocyte-macrophage colony-stimulating factor messenger RNA deadenylation and stability
    E Carballo
    Office of Clinical Research and Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
    Blood 95:1891-9. 2000
    ..TTP appears to be a physiological regulator of GM-CSF mRNA deadenylation and stability. (Blood. 2000;95:1891-1899)..
  77. pmc Oligomerized pool engineering (OPEN): an 'open-source' protocol for making customized zinc-finger arrays
    Morgan L Maeder
    Molecular Pathology Unit, Center for Cancer Research, and Center for Computational and Integrative Biology, Massachusetts General Hospital, Charlestown, Massachusetts, USA
    Nat Protoc 4:1471-501. 2009
    ..Here we provide a detailed protocol for carrying out OPEN to engineer zinc-finger arrays that have a high probability of functioning as ZFNs. Using OPEN, researchers can generate multiple, customized ZFNs in approximately 8 weeks...
  78. ncbi The discovery of zinc fingers and their development for practical applications in gene regulation and genome manipulation
    Aaron Klug
    MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK
    Q Rev Biophys 43:1-21. 2010
    ..b>Zinc fingers were discovered in 1985, arising from the interpretation of our biochemical studies on the interaction of the ..
  79. pmc Evidence that tristetraprolin binds to AU-rich elements and promotes the deadenylation and destabilization of tumor necrosis factor alpha mRNA
    W S Lai
    Office of Clinical Research and Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
    Mol Cell Biol 19:4311-23. 1999
    ..We show here that TTP binding to the TNF-alpha ARE is dependent upon the integrity of both zinc fingers, since mutation of a single cysteine residue in either zinc finger to arginine severely attenuated the binding ..
  80. pmc Targeted plasmid integration into the human genome by an engineered zinc-finger recombinase
    Charles A Gersbach
    The Skaggs Institute for Chemical Biology, Department of Molecular Biology, CA, USA
    Nucleic Acids Res 39:7868-78. 2011
    ..This work demonstrates the potential for broad applicability of the ZFR technology in genome engineering, synthetic biology and gene therapy...
  81. pmc Gain, loss and divergence in primate zinc-finger genes: a rich resource for evolution of gene regulatory differences between species
    Katja Nowick
    Institute for Genomic Biology, University of Illinois, Urbana, Illinois, United States of America
    PLoS ONE 6:e21553. 2011
    ..The large species differences in this family of TFs stands in stark contrast to the overall high conservation of primate genomes and potentially represents a potent driver of primate evolution...
  82. pmc Functional analysis of a novel Cys2/His2-type zinc finger protein involved in salt tolerance in rice
    Shu Jing Sun
    National Key Laboratory of Crop Genetics and Germplasm Enhancement, College of Agriculture, Nanjing Agricultural University, Nanjing, China
    J Exp Bot 61:2807-18. 2010
    ..Our studies suggest that ZFP179 plays a crucial role in the plant response to salt stress, and is useful in developing transgenic crops with enhanced tolerance to salt stress...
  83. pmc Specific implications of the HIV-1 nucleocapsid zinc fingers in the annealing of the primer binding site complementary sequences during the obligatory plus strand transfer
    Julien Godet
    Laboratoire de Biophotonique et Pharmacologie, UMR 7213 CNRS, Universite de Strasbourg, Faculte de Pharmacie, 74 route du Rhin, 67401 Illkirch, France
    Nucleic Acids Res 39:6633-45. 2011
    ..Our data suggest that the two NCp7 zinc fingers are required to ensure the specificity and fidelity of the second strand transfer, further underlining the ..
  84. ncbi Standardized reagents and protocols for engineering zinc finger nucleases by modular assembly
    David A Wright
    Department of Genetics, Development and Cell Biology, Iowa State University, 1035A Roy J Carver Co Lab, Ames, Iowa 50011, USA
    Nat Protoc 1:1637-52. 2006
    ..We also describe a bacterial cell-based reporter assay for rapidly screening the DNA-binding activities of assembled multi-finger arrays. This protocol can be completed in approximately 24-26 d...
  85. pmc Oxidase-deficient neutrophils from X-linked chronic granulomatous disease iPS cells: functional correction by zinc finger nuclease-mediated safe harbor targeting
    Jizhong Zou
    Division of Hematology, Department of Medicine, and Stem Cell Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    Blood 117:5561-72. 2011
    ..Our findings demonstrate how precise gene targeting may be applied to correction of X-CGD using zinc finger nuclease and patient iPSCs...
  86. ncbi CTCF mediates methylation-sensitive enhancer-blocking activity at the H19/Igf2 locus
    A T Hark
    Howard Hughes Medical Institute and Department of Molecular Biology, Princeton University, New Jersey 08544, USA
    Nature 405:486-9. 2000
    ..Consistent with our model, CTCF binding is abolished by DNA methylation. This is the first example, to our knowledge, of a regulated chromatin boundary in vertebrates...
  87. pmc Modular system for the construction of zinc-finger libraries and proteins
    Beatriz Gonzalez
    The Skaggs Institute for Chemical Biology, La Jolla, California, USA
    Nat Protoc 5:791-810. 2010
    ..We also describe the construction of a customized ZF-TF that can be transferred to a number of expression vectors. This protocol can be completed in 9-11 d...
  88. ncbi Interactions of CCCH zinc finger proteins with mRNA: non-binding tristetraprolin mutants exert an inhibitory effect on degradation of AU-rich element-containing mRNAs
    Wi S Lai
    Office of Clinical Research and the Laboratory of Signal Transduction, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 277:9606-13. 2002
    ..These data suggest that TTP may act, at least in part, by physically interacting with an enzyme activity or protein complex and functionally stimulating its ability to deadenylate class II ARE-containing mRNAs...
  89. ncbi The BCL11 gene family: involvement of BCL11A in lymphoid malignancies
    E Satterwhite
    Academic Department of Haematology and Cytogenetics, Haddow Laboratories, Institute of Cancer Research, Sutton, United Kingdom
    Blood 98:3413-20. 2001
    ..There were 3 major RNA isoforms of BCL11A, differing in the number of carboxy-terminal zinc fingers. All 3 RNA isoforms were deregulated as a consequence of t(2;14)(p13;q32.3)...
  90. ncbi Meganucleases and DNA double-strand break-induced recombination: perspectives for gene therapy
    Frédéric Pâques
    Cellectis SA, 102, route de Noisy, 93 340 Romainville Cedex France
    Curr Gene Ther 7:49-66. 2007
    ..Finally, we will discuss the main issues that will need to be addressed in order to bring this promising technology to the patient...
  91. pmc Genome-wide analysis of KAP1 binding suggests autoregulation of KRAB-ZNFs
    Henriette O'Geen
    Department of Pharmacology, University of California Davis, Davis, California, United States of America
    PLoS Genet 3:e89. 2007
    ..Because KAP1 is recruited to the DNA via interaction with KRAB-ZNF proteins, we suggest that expression of KRAB-ZNF genes may be controlled via an auto-regulatory mechanism involving KAP1...
  92. pmc High frequency targeted mutagenesis in Arabidopsis thaliana using zinc finger nucleases
    Feng Zhang
    Department of Genetics, Cell Biology, and Development and Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA
    Proc Natl Acad Sci U S A 107:12028-33. 2010
    ..Taken together, our results suggest that it should now be possible to obtain mutations in any Arabidopsis target gene regardless of its mutant phenotype...
  93. pmc Bassoon, a novel zinc-finger CAG/glutamine-repeat protein selectively localized at the active zone of presynaptic nerve terminals
    S tom Dieck
    Leibniz Institute for Neurobiology, D 39118 Magdeburg, Germany
    J Cell Biol 142:499-509. 1998
    ..The Bassoon protein is predicted to contain two double-zinc fingers, several coiled-coil domains, and a stretch of polyglutamines (24 and 11 residues in rat and mouse, ..
  94. pmc Attenuation of zinc finger nuclease toxicity by small-molecule regulation of protein levels
    Shondra M Pruett-Miller
    Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America
    PLoS Genet 5:e1000376. 2009
    ..We show that by regulating protein levels, we can maintain high rates of ZFN-mediated gene targeting while reducing ZFN toxicity...
  95. ncbi Feedback inhibition of macrophage tumor necrosis factor-alpha production by tristetraprolin
    E Carballo
    Office of Clinical Research and Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
    Science 281:1001-5. 1998
    ..These findings identify TTP as a component of a negative feedback loop that interferes with TNF-alpha production by destabilizing its messenger RNA. This pathway represents a potential target for anti-TNF-alpha therapies...
  96. pmc Expanding or restricting the target site repertoire of zinc-finger nucleases: the inter-domain linker as a major determinant of target site selectivity
    Eva Maria Händel
    Charite Medical School, Institute of Virology CBF, Berlin, Germany
    Mol Ther 17:104-11. 2009
    ..In summary, both sequence and length of the inter-domain linker determine ZFN activity and target-site specificity, and are therefore important parameters to account for when designing ZFNs for genome editing...
  97. pmc Directed evolution of recombinase specificity by split gene reassembly
    Charles A Gersbach
    The Skaggs Institute for Chemical Biology, Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Nucleic Acids Res 38:4198-206. 2010
    ..This enhanced evolution system will translate recombinase engineering and genome editing into a practical and expedient endeavor for academic, industrial and clinical applications...
  98. pmc Predicting DNA recognition by Cys2His2 zinc finger proteins
    Anton V Persikov
    Lewis Sigler Institute for Integrative Genomics and Department of Computer Science, Princeton University, Princeton, NJ 08544, USA
    Bioinformatics 25:22-9. 2009
    ..The 'canonical model' for ZF protein-DNA interaction consists of only four amino acid nucleotide contacts per zinc finger domain...
  99. pmc An affinity-based scoring scheme for predicting DNA-binding activities of modularly assembled zinc-finger proteins
    Jeffry D Sander
    Department of Genetics, Development and Cell Biology, Bioinformatics and Computational Biology Program, Iowa State University, Ames, IA 50011, USA
    Nucleic Acids Res 37:506-15. 2009
    ..91). We propose that success rates for ZFP modular assembly can be significantly improved by exploiting the score-based strategy described here...
  100. pmc Sensing peptide-oligonucleotide interactions by a two-color fluorescence label: application to the HIV-1 nucleocapsid protein
    Volodymyr V Shvadchak
    Laboratoire de Biophotonique et Pharmacologie, Faculte de Pharmacie, UMR 7213 du CNRS, Universite de Strasbourg, 67401 Illkirch, France
    Nucleic Acids Res 37:e25. 2009
    ..The described methodology could become a new universal tool for investigating peptide-ODN interactions...
  101. pmc Antagonistic control of oxidative stress-induced cell death in Arabidopsis by two related, plant-specific zinc finger proteins
    Petra Epple
    Department of Biology, Coker Hall 108, CB 3280, University of North Carolina, Chapel Hill 27599 3280, USA
    Proc Natl Acad Sci U S A 100:6831-6. 2003
    ..We also show that LSD1 and LOL1 have antagonistic effects on copper-zinc superoxide dismutase accumulation, consistent with functions in cell death control via maintenance of ROI homeostasis...

Research Grants62

  1. Arsenic co-carcinogenesis with UVR: nitrosation and oxidation of target proteins
    Ke Jian Liu; Fiscal Year: 2013
    ..Aim 2 will investigate the interaction of arsenic-generated reactive oxygen and nitrogen species with the zinc fingers of XPA and PARP-1 and apply analytical techniques to define specific modifications of the zinc finger domain ..
  2. Transcriptional regulation of proteinuria
    SUMANT SINGH CHUGH; Fiscal Year: 2011
    ..The goal of this proposal is to understand the role of transcriptional factor Zinc Fingers and Homeoboxes 3 (ZHX3) in the pathogenesis of glomerular disease...
  3. Prostate cancer prevention by selenium supplementation
    Rayudu Gopalakrishna; Fiscal Year: 2012
    ..exert their cancer-preventive actions, at least in part, through oxidation of unique cysteine- rich regions and zinc fingers present in protein kinase C (PKC), a known target for a variety of tumor promoters...
  4. Recognition of Regulatory and Pathogenic RNA by Muscleblind Zinc Fingers
    PETER EDWIN WRIGHT; Fiscal Year: 2010
    ..The interactions of the human muscleblind zinc fingers with single stranded RNA targets and with double stranded CUG and CCUG repeats will be mapped using NMR and ..
  5. Promoter Specific Hypermethylation Sensors for Early Cancer Detection
    Indraneel Ghosh; Fiscal Year: 2011
    ..This approach if successful will rapidly distinguish between normal and cancerous tissues in a clinical setting without the requirement for bisulfite treatment, PCR amplification, and sequencing. ..
  6. NextGen DNA Binding Proteins Based on TAL Domains
    David J Segal; Fiscal Year: 2013
    ..TAL domains appear to be even more flexible in their recognition properties than zinc fingers (ZFs), the engineering of which have had transformative impact in the areas of gene regulation, genome ..
  7. Prediction and Design of Nucleic Acid Recognition by Repeat Proteins
    Philip Bradley; Fiscal Year: 2013
    ..TPR, ankyrin, and HEAT repeat proteins have been selected for use in protein-protein interactions, while C2H2 zinc fingers, PUF, and PPR repeats are widely deployed for sequence-specific recognition of nucleic acids...
  8. Control of lymphoid effector programs by the E3 ligase cullin 3
    ALBERT S BENDELAC; Fiscal Year: 2013
    ..their BTB domain in order to induce chromatin modifications at sequence-specific target sites bound by their zinc fingers. PLZF directs the developmental acquisition of innate-like effector properties by microbial lipid-specific NKT ..
  9. A unique double PHD finger and bromodomain in epigenetic signaling
    KAREN CHAMPAGNE GLASS; Fiscal Year: 2013
    ....
  10. Biological functions and mechanisms of action of Ikaros proteins
    Stephen T Smale; Fiscal Year: 2013
    ..the approximately 800 C2H2 zinc finger proteins encoded by mammalian genomes, Ikaros contains multiple tandem zinc fingers within its DNA-binding domain...
  11. Assessment of the Chemical Biology of HNO via New Donors
    Katrina M Miranda; Fiscal Year: 2010
    ..Additionally, new biological targets, such as zinc fingers and non-heme iron centers, are likely to be revealed, which may suggest other therapeutic interventions.
  12. METALLOENZYME SYNTHESIS, STRUCTURE AND FUNCTION
    William Konigsberg; Fiscal Year: 1999
    ..functional roles of Zn(II) in 1) zinc metalloenzymes, 2) the eukaryotic transcription factors originally termed zinc fingers, and 3) several proteins involved in nucleic acid replication which contain zinc...
  13. PROMYELOCYTIC ZINC FINGER GENE
    Jennifer Morris; Fiscal Year: 1999
    ..Recombinant PLZF protein containing the nine C2H2 zinc fingers will be used to affinity select (by gel shift assays or chromatography) DNA binding sites from a degenerate ..
  14. 800 MHz Spectrometer for Biomolecular NMR in Missouri
    STEVEN VAN DOREN; Fiscal Year: 2006
    ..He will study all six of its zinc fingers free and bound to DNA...
  15. NMR STUDIES OF RETROVIRAL NUCLEIC ACID BINDING PROTEINS
    Michael Summers; Fiscal Year: 1993
    ..Although zinc fingers from DNA-binding proteins have received much recent attention, important questions exist regarding the ..
  16. MOLECULAR MECHANISMS IN EVI1-INDUCED MYELOID LEUKEMIA
    Archibald Perkins; Fiscal Year: 2000
    ..is known to bind with high specificity to two sequences (GACAAGATA and GAAGATGAG) via two separate domains of zinc fingers, although the target genes on which it acts have not been described...
  17. SYNTHESIS ANTI-HIV AGENTS THAT TARGET ZINC FINGERS
    MARK WELKER; Fiscal Year: 2000
    ..of new sulfur heterocycles which will chemically modify the nucleophilic cysteine residues in the NCp7 zinc fingers. All new heterocycles produced will be screened in collaboration with Dr...
  18. Transcriptional regulation of proteinuria
    Sumant Chugh; Fiscal Year: 2007
    ..The overall goal of this proposal is to understand the role of transcriptional factor Zinc Fingers and Homeoboxes 3 (ZHX3) in the pathogenesis of proteinuria...
  19. NOVEL KRUPPEL-GENES TEMPORALLY EXPRESSED IN NEPHROGENES
    Jesus Lopez Guisa; Fiscal Year: 2002
    ..Ultimately, this research will expose the potential for gene therapies to overcome--or even prevent--kidney failure. ..
  20. FOG1 AND HEMATOPOIESIS
    Alan Cantor; Fiscal Year: 2003
    ..protein, termed FOG for Friend of GATA-1, is a 995 amino acid protein that contains nine predicted multitype zinc fingers. It is co-expressed with GATA-1 during embryonic development...
  21. MULTIPLE CHIMERIC TRANSCRIPTS IN THE T(3--21)
    Giuseppina Nucifora; Fiscal Year: 1999
    ....
  22. Targets of Ewing Sarcoma-Wilms Tumor 1 Oncoprotein
    Daniel Haber; Fiscal Year: 2006
    ..fusing the N-terminal transactivational domain (NTD) of the Ewing Sarcoma gene EWS to the three C-terminal zinc fingers of the Wilms tumor suppressor gene WT1, whose DNA binding domain is modulated by alternative splicing (plus/..
  23. PROGRESSION OF T CELL LYMPHOMA LINES TO IL2 INDEPENDENCE
    Philip Tsichlis; Fiscal Year: 2001
    ..The long term objective of this project is to use Gfi-1 and Gfi-1B as probes to explore the biology of the hematopoietic system and the pathobiology of neoplasia with emphasis on cell cycle progression differentiation and apoptosis. ..
  24. DESIGNER DNA BINDING PROTEINS TARGETING HIV GENES
    Andrew Jamieson; Fiscal Year: 1999
    b>Zinc fingers are a class of DNA binding proteins that can be designed to recognize DNA sequences according to a recently devised recognition code...
  25. Zinc Transporters and Intracellular Zinc Trafficking
    David Eide; Fiscal Year: 2007
    ..Zinc is a catalytic cofactor of over 300 enzymes and is a critical component of structural motifs such as zinc fingers. Therefore, cells require efficient mechanisms for the accumulation of zinc...
  26. DNA-binding specificities of Cys2His2 zinc fingers
    J Keith Joung; Fiscal Year: 2010
    ..and to use this comprehensive dataset to develop and validate probabilistic DMA-recognition codes for Cys2His2 zinc fingers with greatly improved predictive power...
  27. Functions of the SNAG Repression Domain in Oncogenesis
    Frank Rauscher; Fiscal Year: 2007
    ..The SNAG-ZF family in vertebrates share a COOH-terminal DNA binding domain composed of 5 -7 Cys2-His2 zinc fingers and a highly conserved NH2- terminus which contains the 21 amino acid SNAG repression domain...
  28. PARAMAGNETIC IONS USE IN NMR STRUCTURE DETERMINATION
    Miriam Gochin; Fiscal Year: 1999
    ..3) Pseudocontact shifts in zinc fingers with cobalt substitution for zinc will be studies for their potential in athe definition of zinc fingers and ..
  29. Differential Functions of Sp-Family Members
    Jonathan Horowitz; Fiscal Year: 2006
    ..In so doing, we will link specific Sp-family members and their regulators with extracellular signals that govern the synthesis of Sp-dependent genes. ..
  30. ZINC FINGERS IN KIDNEY DEVELOPMENT
    ERIC NEILSON; Fiscal Year: 1999
    ..We propose to look for other new zinc fingers that are active in embryonic murine kidney...
  31. TRANSCRIPTIONAL REGULATORS IN CHONDROGENESIS
    Brendan Lee; Fiscal Year: 1999
    ....
  32. TRANSCRIPTIONAL REGULATORS IN CHONDROGENESIS
    Brendan Lee; Fiscal Year: 2002
    ....
  33. NMR STRUCTURE OF ZINC FINGERS SPECIFIC FOR HIV RRE RNA
    Markus Germann; Fiscal Year: 2005
    ..To enhance and further understand the RNA binding properties of zinc fingers, a design process will use structural information to guide in vitro selection as well as traditional site ..
  34. RNA Targets of the Wilm's Tumor Protein in the Kidney
    Russ Carstens; Fiscal Year: 2005
    ..in proteins that contain [WT1(+KTS)] or exclude [WT1(-KTS)] three amino acids between the third and fourth zinc fingers appear to have distinct functions in the nucleus of expressing cells...
  35. PIE-1 GENE AND GERM CELL DETERMINATION IN C ELEGANS
    Craig Mello; Fiscal Year: 1999
    ....
  36. Translational Control of Early Neurogenesis in Drosophila
    Fen Biao Gao; Fiscal Year: 2009
    ..Senseless (Sens), a nuclear protein with four zinc fingers that is required to upregulate and maintain proneural gene expression in SOPs, is expressed at a high level in ..
  37. CYTOKINE MODULATION OF ENDOTHELIAL GENE EXPRESSION
    Vishva Dixit; Fiscal Year: 1992
    ..Importantly, one of these (A20) contains seven zinc fingers which is characteristic of a certain class of transcriptional factors...
  38. SPECTROSCOPY OF HEAVY ATOM PERTURBED BIOPOLYMERS
    AUGUST MAKI; Fiscal Year: 2000
    ..b>Zinc fingers have been found to undergo base-stacking with model RNAs. Similar interactions will be sought...
  39. Specificity of Protein-DNA/RNA Interactions
    JOEL GOTTESFELD; Fiscal Year: 2004
    ..These methods will be applied to the RNA-specific zinc fingers of TFIIIA in order to understand the molecular basis for RNA-binding and to basic helix-loop-helix proteins to ..
  40. GATA Factor-Specific Transcriptional Regulation
    KIRBY JOHNSON; Fiscal Year: 2007
    ..Aim 1. To determine how GATA-1 and GATA-2 elicit similar and distinct transcriptional responses. The zinc fingers of GATA factors are crucial for function and are well conserved among GATA family members...
  41. Poxvirus/host interactions of the D4R virulence factor
    Todd Gray; Fiscal Year: 2003
    ..abstract_text> ..
  42. Effect of APOBEC3G on retroviruses and retrotransposons
    BRYAN CULLEN; Fiscal Year: 2009
    ..packages into PFV virions is unclear, as PFV Gag does not contain sequences related to the HIV-1 nucleocapsid zinc fingers implicated in virion packaging of APOBEC3G...
  43. THE JAZF1 AND 2 GENES IN UTERINE SARCOMAS
    Jeffrey Sklar; Fiscal Year: 2005
    ..domains, and in JAZF1, the sequences of codons for two such domains closely resemble the sequence for two zinc fingers found in the transcription factor Sfplp, which has recently been implicated in the mechanism governing the G2/M ..
  44. MALE GERM CELL-AFFECTING GENES ON MOUSE CHROMOSOME 17
    Masanori Kasahara; Fiscal Year: 1991
    ..for by their mutations. In this sense, the proposed project has direct clinical relevance and should provide us with basic knowledge that should lead to better diagnosis and treatment of human male infertility...
  45. BCL11 GENES IN NORMAL AND MALIGNANT B CELL DEVELOPMENT
    Philip Tucker; Fiscal Year: 2005
    ..There are three common BCL11A isoforms; each is a transcriptional repressor and varies in the number of zinc fingers. BCL11A interacts physically with and shares several similarities with BCL6, a gene frequently translocated to ..
  46. OTK18 Regulation in HIV-1 associated dementia
    Tsuneya Ikezu; Fiscal Year: 2009
    ..findings may also have an important impact in the field of zinc finger molecules, since OTK18 is located on chromosome 19q13, where clusters of retroviral integration sites and zinc fingers are evolutionally co-localized.
  47. Using Zinc Finger Nucleases to Stimulate Gene Targeting in HSC
    Matthew Porteus; Fiscal Year: 2009
    ..abstract_text> ..
  48. Stimulating Gene Targeting with Zinc Finger Nucleases
    Dana Carroll; Fiscal Year: 2004
    ..b>Zinc fingers that recognize new sequences can be generated by changing the identity of a few amino acids that contact the ..
  49. Development of gene targeting in C. elegans and D. rerio using zinc finger
    Matthew Porteus; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  50. Chimeric Nucleases for Gene Targeting in Drosophila
    Dana Carroll; Fiscal Year: 2003
    ..We are working with chimeric nucleases that combine a DNA-binding domain comprised of zinc fingers with a nonspecific DNA-cleavage domain...
  51. The Genetics of Gene Targeting in Vertebrate Cells
    Matthew Porteus; Fiscal Year: 2006
    ..It is hoped that such studies will lead to advances in the field of gene therapy and in the treatment of children with monogenic diseases, such as sickle cell disease. ..
  52. NEURAL CONTROL OF A MOTOR PROGRAM
    James Thomas; Fiscal Year: 2002
    ..We will also continue genetic screens to identify additional potential targets. ..
  53. Using Enhanced Gene Targeting to Repair the Sickle Cell
    Fyodor Urnov; Fiscal Year: 2004
    ..While this study focuses on SCD, this approach represents a dramatic advance for the repair of any genetic point lesion. ..
  54. ZFN-driven Gene Disruption of CCR5 as a Potential Treatment of AIDS
    Fyodor Urnov; Fiscal Year: 2006
    ..unreadable] [unreadable] [unreadable]..
  55. GENETIC ANALYSIS OF CHEMOSENSATION IN C ELEGANS
    James Thomas; Fiscal Year: 2003
    ..All of the pathways under study here correspond to important regulatory pathways in humans, and many of the genes are affected in various inherited disorders. ..
  56. Proteogenomic Analysis of C. elegans
    James Thomas; Fiscal Year: 2007
    ..elegans proteome and a high-throughput pipeline that will allow similar analysis of any complex animal or plant proteome whose genome sequence is available. [unreadable] [unreadable] [unreadable]..
  57. A bacterial one-hybrid system for analyzing DNA-binding specificities
    SCOT WOLFE; Fiscal Year: 2007
    ..The resulting database of information on transcription factors will be valuable for deciphering the mechanisms of gene regulation in higher eukaryotes. [unreadable] [unreadable] [unreadable]..
  58. METALLOTHIONEIN IN REPRODUCTION AND DEVELOPMENT
    Glen Andrews; Fiscal Year: 2002
    ..A testable hypothesis is that misexpression of MT will alter metal homeostasis during pregnancy causing increased sensitivity to dietary Zn deficiency and reduced sensitivity to Cd toxicity. ..
  59. KS1, A NOVEL SUPPRESSOR OF NEOPLASTIC TRANSFORMATION
    Raul Urrutia; Fiscal Year: 2003
    ..This knowledge will serve as the foundation for future studies aimed at using these proteins as therapeutic tools for controlling abnormal cell growth. ..
  60. Systematic Analysis of Drosophila transcription factor binding specificities
    SCOT A contact WOLFE; Fiscal Year: 2010
    ..This new genome "map" will help researchers understand how these elements function in normal cells and how mutations in these elements can lead to disease. ..
  61. The Role of Zinc Finger Genes in Pancreatic Cell Growth
    Raul Urrutia; Fiscal Year: 2008
    ..Project Description Page 6 Principal Investigator/Program Director (Last, first, middle): Urrutia, Raul ..
  62. Altering Gastric Epithelial Cell Differentiation
    Juanita Merchant; Fiscal Year: 2007
    ..These studies will further our understanding of how corpus atrophy predisposes the gastric mucosa to neoplastic transformation. [unreadable] [unreadable]..