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

Journal Article · · Genome Research
 [1];  [2];  [2];  [3];  [2];  [4];  [2];  [2];  [4];  [4];  [2];  [2];  [2];  [2];  [5];  [6];  [7];  [3];  [2];  [8]
  1. Univ. of Massachusetts, Worcester, MA (United States). Medical School. Program in Gene Function and Expression; DOE/OSTI
  2. Univ. of Massachusetts, Worcester, MA (United States). Medical School. Program in Gene Function and Expression
  3. Washington Univ., St. Louis, MO (United States). School of Medicine. Dept. of Genetics
  4. Univ. of Illinois at Urbana-Champaign, IL (United States). Dept. of Computer Science
  5. Univ. of Massachusetts, Worcester, MA (United States). Medical School. Program in Gene Function and Expression; Univ. of Massachusetts, Worcester, MA (United States). Medical School. Dept. of Molecular Medicine; Univ. of Massachusetts, Worcester, MA (United States). Medical School. Program in Bioinformatics and Integrative Biology
  6. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Dept. of Genome Dynamics
  7. Univ. of Illinois at Urbana-Champaign, IL (United States). Dept. of Computer Science; Univ. of Illinois at Urbana-Champaign, IL (United States). Inst. for Genomic Biology
  8. Univ. of Massachusetts, Worcester, MA (United States). Medical School. Program in Gene Function and Expression; Univ. of Massachusetts, Worcester, MA (United States). Dept. of Biochemistry and Molecular Pharmacology

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.

Research Organization:
Univ. of California, Oakland, CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
Grant/Contract Number:
AC02-05CH11231
OSTI ID:
1625622
Journal Information:
Genome Research, Journal Name: Genome Research Journal Issue: 6 Vol. 23; ISSN 1088-9051
Publisher:
Cold Spring Harbor Laboratory PressCopyright Statement
Country of Publication:
United States
Language:
English

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Widespread evidence of cooperative DNA binding by transcription factors in Drosophila development journal July 2013
De novo prediction of DNA-binding specificities for Cys2His2 zinc finger proteins journal October 2013
An improved predictive recognition model for Cys2-His2 zinc finger proteins journal February 2014
A systematic survey of the Cys2His2 zinc finger DNA-binding landscape journal January 2015
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DIVERSITY in binding, regulation, and evolution revealed from high-throughput ChIP journal April 2017
Spatially varying cis-regulatory divergence in Drosophila embryos elucidates cis-regulatory logic posted_content November 2017
Mutation of sequences flanking and separating transcription factor binding sites in a Drosophila enhancer significantly alter its output posted_content July 2018
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Social isolation-induced epigenetic and transcriptional changes in Drosophila dopaminergic neurons posted_content October 2018
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Spatial expression of transcription factors in Drosophila embryonic organ development journal January 2013
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cis-regulatory variation modulates susceptibility to enteric infection in the Drosophila genetic reference panel journal January 2020
Glass confers rhabdomeric photoreceptor identity in Drosophila, but not across all metazoans journal March 2019
iRegulon: From a Gene List to a Gene Regulatory Network Using Large Motif and Track Collections journal July 2014
DIVERSITY in binding, regulation, and evolution revealed from high-throughput ChIP journal April 2018
Spatially varying cis-regulatory divergence in Drosophila embryos elucidates cis-regulatory logic journal November 2018
Cys2/His2 Zinc-Finger Proteins in Transcriptional Regulation of Flower Development journal August 2018
Conservation of transcription factor binding specificities across 600 million years of bilateria evolution journal March 2015