Global analysis of Drosophila Cys2-His2 zinc finger proteins reveals a multitude of novel recognition motifs and binding determinants
Authors
Enuameh, Metewo SelaseAsriyan, 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.
UMass Chan Affiliations
Department of Biochemistry and Molecular PharmacologyProgram in Molecular Medicine
Program in Gene Function and Expression
Document Type
Journal ArticlePublication Date
2013-06-01Keywords
Zinc FingersDrosophila Proteins
DNA-Binding Proteins
Gene Regulatory Networks
Genetics and Genomics
Genomics
Molecular Genetics
Metadata
Show full item recordAbstract
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 siteDOI
10.1101/gr.151472.112Permanent Link to this Item
http://hdl.handle.net/20.500.14038/30634PubMed ID
23471540Related Resources
Link to Article in PubMedRights
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