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

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 artificialmore » fingers can be used to create functional zinc finger nucleases for editing vertebrate genomes.« less

Authors:
 [1];  [1];  [1];  [2];  [1];  [3];  [1];  [1];  [3];  [3];  [1];  [1];  [1];  [1];  [4];  [5];  [6];  [2];  [1];  [7]
  1. Univ. of Massachusetts, Worcester, MA (United States). Medical School. Program in Gene Function and Expression
  2. Washington Univ., St. Louis, MO (United States). School of Medicine. Dept. of Genetics
  3. Univ. of Illinois at Urbana-Champaign, IL (United States). Dept. of Computer Science
  4. 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
  5. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Dept. of Genome Dynamics
  6. 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
  7. 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
Publication Date:
Research Org.:
Univ. of California, Oakland, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
OSTI Identifier:
1625622
Grant/Contract Number:  
AC02-05CH11231
Resource Type:
Accepted Manuscript
Journal Name:
Genome Research
Additional Journal Information:
Journal Volume: 23; Journal Issue: 6; Journal ID: ISSN 1088-9051
Publisher:
Cold Spring Harbor Laboratory Press
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity

Citation Formats

Enuameh, Metewo S., Asriyan, Y., Richards, A., Christensen, R. G., Hall, V. L., Kazemian, M., Zhu, C., Pham, H., Cheng, Q., Blatti, C., Brasefield, J. A., Basciotta, M. D., Ou, J., McNulty, J. C., Zhu, L. J., Celniker, S. E., Sinha, S., Stormo, G. D., Brodsky, M. H., and Wolfe, S. A. Global analysis of Drosophila Cys2-His2 zinc finger proteins reveals a multitude of novel recognition motifs and binding determinants. United States: N. p., 2013. Web. doi:10.1101/gr.151472.112.
Enuameh, Metewo S., Asriyan, Y., Richards, A., Christensen, R. G., Hall, V. L., Kazemian, M., Zhu, C., Pham, H., Cheng, Q., Blatti, C., Brasefield, J. A., Basciotta, M. D., Ou, J., McNulty, J. C., Zhu, L. J., Celniker, S. E., Sinha, S., Stormo, G. D., Brodsky, M. H., & Wolfe, S. A. Global analysis of Drosophila Cys2-His2 zinc finger proteins reveals a multitude of novel recognition motifs and binding determinants. United States. https://doi.org/10.1101/gr.151472.112
Enuameh, Metewo S., Asriyan, Y., Richards, A., Christensen, R. G., Hall, V. L., Kazemian, M., Zhu, C., Pham, H., Cheng, Q., Blatti, C., Brasefield, J. A., Basciotta, M. D., Ou, J., McNulty, J. C., Zhu, L. J., Celniker, S. E., Sinha, S., Stormo, G. D., Brodsky, M. H., and Wolfe, S. A. Thu . "Global analysis of Drosophila Cys2-His2 zinc finger proteins reveals a multitude of novel recognition motifs and binding determinants". United States. https://doi.org/10.1101/gr.151472.112. https://www.osti.gov/servlets/purl/1625622.
@article{osti_1625622,
title = {Global analysis of Drosophila Cys2-His2 zinc finger proteins reveals a multitude of novel recognition motifs and binding determinants},
author = {Enuameh, Metewo S. and Asriyan, Y. and Richards, A. and Christensen, R. G. and Hall, V. L. and Kazemian, M. and Zhu, C. and Pham, H. and Cheng, Q. and Blatti, C. and Brasefield, J. A. and Basciotta, M. D. and Ou, J. and McNulty, J. C. and Zhu, L. J. and Celniker, S. E. and Sinha, S. and Stormo, G. D. and Brodsky, M. H. and Wolfe, S. A.},
abstractNote = {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.},
doi = {10.1101/gr.151472.112},
journal = {Genome Research},
number = 6,
volume = 23,
place = {United States},
year = {Thu Mar 07 00:00:00 EST 2013},
month = {Thu Mar 07 00:00:00 EST 2013}
}

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De novo prediction of DNA-binding specificities for Cys2His2 zinc finger proteins
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Social isolation-induced epigenetic and transcriptional changes in Drosophila dopaminergic neurons
posted_content, October 2018

  • Agarwal, Pavan; Chung, Phuong; Heberlein, Ulrike
  • BMC Biology
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Diversification of transcription factor-DNA interactions and the evolution of gene regulatory networks
journal, April 2018

  • Rogers, Julia M.; Bulyk, Martha L.
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A protein-RNA specificity code enables targeted activation of an endogenous human transcript
journal, June 2014

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Spatially varying cis-regulatory divergence in Drosophila embryos elucidates cis-regulatory logic
posted_content, November 2017

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  • PLOS Genetics
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An improved predictive recognition model for Cys2-His2 zinc finger proteins
journal, February 2014

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Deciphering the DNA code for the function of the Drosophila polydactyl zinc finger protein Suppressor of Hairy-wing
journal, February 2017

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Spatial expression of transcription factors in Drosophila embryonic organ development
journal, January 2013


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


DIVERSITY in binding, regulation, and evolution revealed from high-throughput ChIP
journal, April 2017

  • Mitra, Sneha; Biswas, Anushua; Narlikar, Leelavati
  • PLOS Computational Biology
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Review of CRISPR/Cas9 sgRNA Design Tools
journal, April 2018

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A systematic survey of the Cys2His2 zinc finger DNA-binding landscape
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Broad-complex, tramtrack, and bric-à-brac (BTB) proteins: Critical regulators of development: C haharbakhshi and J emc
journal, August 2016

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cis-regulatory variation modulates susceptibility to enteric infection in the Drosophila genetic reference panel
journal, January 2020

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Cys2/His2 Zinc-Finger Proteins in Transcriptional Regulation of Flower Development
journal, August 2018

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iRegulon: From a Gene List to a Gene Regulatory Network Using Large Motif and Track Collections
journal, July 2014


Widespread evidence of cooperative DNA binding by transcription factors in Drosophila development
journal, July 2013

  • Kazemian, Majid; Pham, Hannah; Wolfe, Scot A.
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Glass confers rhabdomeric photoreceptor identity in Drosophila, but not across all metazoans
journal, March 2019


Glass confers rhabdomeric photoreceptor identity in Drosophila , but not across all metazoans
posted_content, February 2019

  • Bernardo-Garcia, F. Javier; Syed, Maryam; Jékely, Gáspár
  • EvoDevo
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