A Comprehensive Drosophila melanogaster Transcription Factor Interactome
Leila Shokri,
Sachi Inukai,
Antonina Hafner,
Kathryn Weinand,
Korneel Hens,
Anastasia Vedenko,
Stephen S. Gisselbrecht,
Riccardo Dainese,
Johannes Bischof,
Edy Furger,
Jean-Daniel Feuz,
Konrad Basler,
Bart Deplancke,
Martha L. Bulyk
Affiliations
Leila Shokri
Department of Medicine, Division of Genetics, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
Sachi Inukai
Department of Medicine, Division of Genetics, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
Antonina Hafner
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
Kathryn Weinand
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
Korneel Hens
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
Anastasia Vedenko
Department of Medicine, Division of Genetics, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
Stephen S. Gisselbrecht
Department of Medicine, Division of Genetics, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
Riccardo Dainese
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
Johannes Bischof
Institute of Molecular Life Sciences, University of Zurich, 8057 Zurich, Switzerland
Edy Furger
Institute of Molecular Life Sciences, University of Zurich, 8057 Zurich, Switzerland
Jean-Daniel Feuz
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
Konrad Basler
Institute of Molecular Life Sciences, University of Zurich, 8057 Zurich, Switzerland
Bart Deplancke
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; Corresponding author
Martha L. Bulyk
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; Corresponding author
Summary: 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. : Combinatorial regulation by transcription factors (TFs) is one mechanism for achieving condition and tissue-specific gene regulation. Shokri et al. mapped TF-TF interactions between most Drosophila TFs, reporting a comprehensive TF-TF network integrated with previously known interactions. They used this network to discern distinct TF-DNA binding modes. Keywords: transcription factors, Drosophila melanogaster, protein-protein interactions, yeast two-hybrid, transcription factor-DNA interactions, MITOMI, in vivo bimolecular fluorescence complementation assay, BiFC, ChIP-seq analysis
