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A Comprehensive Drosophila melanogaster Transcription Factor Interactome.

Authors
  • Shokri, Leila1
  • Inukai, Sachi1
  • Hafner, Antonina2
  • Weinand, Kathryn3
  • Hens, Korneel4
  • Vedenko, Anastasia1
  • Gisselbrecht, Stephen S1
  • Dainese, Riccardo4
  • Bischof, Johannes5
  • Furger, Edy5
  • Feuz, Jean-Daniel4
  • Basler, Konrad5
  • Deplancke, Bart6
  • Bulyk, Martha L7
  • 1 Department of Medicine, Division of Genetics, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
  • 2 Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA; Systems Biology Graduate Program, Harvard University, Cambridge, MA 02138, USA; Laboratory of Systems Biology and Genetics, Institute of Bioengineering, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland. , (Switzerland)
  • 3 Department of Medicine, Division of Genetics, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Bioinformatics and Integrative Genomics Ph.D. Program, Harvard University, Cambridge, MA 02138, USA.
  • 4 Laboratory of Systems Biology and Genetics, Institute of Bioengineering, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland. , (Switzerland)
  • 5 Institute of Molecular Life Sciences, University of Zurich, 8057 Zurich, Switzerland. , (Switzerland)
  • 6 Laboratory of Systems Biology and Genetics, Institute of Bioengineering, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland. Electronic address: [email protected] , (Switzerland)
  • 7 Department of Medicine, Division of Genetics, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Systems Biology Graduate Program, Harvard University, Cambridge, MA 02138, USA; Bioinformatics and Integrative Genomics Ph.D. Program, Harvard University, Cambridge, MA 02138, USA; Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. Electronic address: [email protected]
Type
Published Article
Journal
Cell Reports
Publisher
Elsevier
Publication Date
Apr 16, 2019
Volume
27
Issue
3
Identifiers
DOI: 10.1016/j.celrep.2019.03.071
PMID: 30995488
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Combinatorial interactions among transcription factors (TFs) play essential roles in generating gene expression specificity and diversity in metazoans. Using yeast 2-hybrid (Y2H) assays on nearly all sequence-specific Drosophila TFs, we identified 1,983 protein-protein interactions (PPIs), more than doubling the number of currently known PPIs among Drosophila TFs. For quality assessment, we validated a subset of our interactions using MITOMI and bimolecular fluorescence complementation assays. We combined our interactome with prior PPI data to generate an integrated Drosophila TF-TF binary interaction network. Our analysis of ChIP-seq data, integrating PPI and gene expression information, uncovered different modes by which interacting TFs are recruited to DNA. We further demonstrate the utility of our Drosophila interactome in shedding light on human TF-TF interactions. This study reveals how TFs interact to bind regulatory elements in vivo and serves as a resource of Drosophila TF-TF binary PPIs for understanding tissue-specific gene regulation. Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

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