University of Massachusetts Medical School Faculty Publications
UMMS Affiliation
Program in Gene Function and Expression; Program in Molecular Medicine;Department of Biochemistry and Molecular Pharmacology
Publication Date
2013-6
Document Type
Article
Subjects
Zinc Fingers; Drosophila Proteins; DNA-Binding Proteins; Gene Regulatory Networks
Disciplines
Genetics and Genomics | Genomics | Molecular Genetics
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.
Rights and Permissions
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/.
DOI of Published Version
10.1101/gr.151472.112
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
Related Resources
Journal/Book/Conference Title
Genome research
PubMed ID
23471540
Repository Citation
Enuameh MS, Asriyan Y, Richards A, Christensen RG, Hall VL, Kazemian M, Zhu C, Pham H, Cheng Q, Blatti C, Brasefield JA, Basciotta MD, Ou J, McNulty JC, Zhu LJ, Celniker SE, Sinha S, Stormo GD, Brodsky MH, Wolfe SA. (2013). Global analysis of Drosophila Cys2-His2 zinc finger proteins reveals a multitude of novel recognition motifs and binding determinants. University of Massachusetts Medical School Faculty Publications. https://doi.org/10.1101/gr.151472.112. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/91