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    Global analysis of Drosophila Cys2-His2 zinc finger proteins reveals a multitude of novel recognition motifs and binding determinants

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    Authors
    Enuameh, Metewo Selase
    Asriyan, Yuna
    Richards, Adam
    Christensen, Ryan G.
    Hall, Victoria L.
    Kazemian, Majid
    Zhu, Cong
    Pham, Hannah
    Cheng, Qiong
    Blatti, Charles
    Brasefield, Jessie A.
    Basciotta, Matthew D.
    Ou, Jianhong
    McNulty, Joseph C.
    Zhu, Lihua Julie
    Celniker, Susan E.
    Sinha, Saurabh
    Stormo, Gary D.
    Brodsky, Michael H.
    Wolfe, Scot A.
    Show allShow less
    UMass Chan Affiliations
    Department of Biochemistry and Molecular Pharmacology
    Program in Molecular Medicine
    Program in Gene Function and Expression
    Document Type
    Journal Article
    Publication Date
    2013-06-01
    Keywords
    Zinc Fingers
    Drosophila Proteins
    DNA-Binding Proteins
    Gene Regulatory Networks
    Genetics and Genomics
    Genomics
    Molecular Genetics
    
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    Link to Full Text
    http://dx.doi.org/10.1101/gr.151472.112
    Abstract
    Cys2-His2 zinc finger proteins (ZFPs) are the largest group of transcription factors in higher metazoans. A complete characterization of these ZFPs and their associated target sequences is pivotal to fully annotate transcriptional regulatory networks in metazoan genomes. As a first step in this process, we have characterized the DNA-binding specificities of 129 zinc finger sets from Drosophila using a bacterial one-hybrid system. This data set contains the DNA-binding specificities for at least one encoded ZFP from 70 unique genes and 23 alternate splice isoforms representing the largest set of characterized ZFPs from any organism described to date. These recognition motifs can be used to predict genomic binding sites for these factors within the fruit fly genome. Subsets of fingers from these ZFPs were characterized to define their orientation and register on their recognition sequences, thereby allowing us to define the recognition diversity within this finger set. We find that the characterized fingers can specify 47 of the 64 possible DNA triplets. To confirm the utility of our finger recognition models, we employed subsets of Drosophila fingers in combination with an existing archive of artificial zinc finger modules to create ZFPs with novel DNA-binding specificity. These hybrids of natural and artificial fingers can be used to create functional zinc finger nucleases for editing vertebrate genomes.
    Source
    Genome Res. 2013 Jun;23(6):928-40. doi: 10.1101/gr.151472.112. Epub 2013 Mar 7. Link to article on publisher's site
    DOI
    10.1101/gr.151472.112
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/30634
    PubMed ID
    23471540
    Related Resources
    Link to Article in PubMed
    Rights
    This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported License), as described at http://creativecommons.org/licenses/by-nc/3.0/.
    ae974a485f413a2113503eed53cd6c53
    10.1101/gr.151472.112
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